Crisis, What Crisis? - Practivism

Sunday, 23 July 2017 11:21 Written by

Here is a copy of the presentation, called "Practivism, it's the new black", given by Dr James Freeman at the International AIDS society meeting in Paris today.

Here is the text that went with the images.

Crisis, What Crisis?

This crisis. Look at this price comparison. I mean seriously?

We only have to look at Egypt to know these medications can be made affordably

Pricing negotiations are one sided and conducted by bandits

Our funders simply can not afford to cover the costs so…

We have rationing that sees only the sickest patients treated

And virtually nothing is being done for high burden populations like prisoners

And People Who Inject Drugs

Politicians pay lip service to the issue

Many advocacy groups are directly funded by Big Pharma*.

And in the Ukraine earlier this year generics were shot down by data exclusivity

Treatment rates are similar to infection rates

In short we are currently going nowhere fast.

Patients are stigmatized and don’t speak out so in the zeitgeist there is no crisis

But we desperately need a new balance between patent rights and patient lives

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And now seven seconds of silence to remember those of us for whom treatment will come too late
One second for each patient who died during the time it's taken to give this presentation

Was it really only 50 years ago our Statesmen talked like this and the crowds came to listen?

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What we call the “big picture” is really just the product of what each and every one of us chooses to do.

What we do as individuals, thinking globally but acting locally, exhibits a butterfly effect so I would like to suggest adopting this butterfly symbol and a simple slogan like "Wear if you care"

Direct Acting Antivirals and Liver Cancer Risk

Saturday, 15 July 2017 01:49 Written by

Over the past year there has been quite a lot of discussion about the risk of liver cancer following treatment with Direct Acting Antivirals like Harvoni® and Sovaldi®.

Here is a quick explanation and the latest thinking from the academic gurus.

First, the risk of Hepatocellular Carcinoma (HCC aka liver cancer) only starts to rise when patients develop cirrhosis, so for patients without cirrhosis there is little to worry about.

In patients with cirrhosis, and untreated Hepatitis C the annual risk of developing liver cancer is 3%. With SVR (cure) following treatment this risk falls to around 1%, so is much less.

In patients who have already had one HCC, treatment increases their short term risk of getting another one (this is probably one they already have but is simply too small to see) and demands very close monitoring both during and immediately after treatment.

So the bottom line is pretty simple. Treat before you get cirrhosis, but if you already have cirrhosis, you are still better off treating. If you have previously had an HCC you can still treat but need very close follow up.

Below you will find the text of a press release from EASL 2017. EASL is the European Association for Study of Liver Diseases and represents the best experts in the world telling it how they see it.

ILC 2017: Is direct-acting antiviral therapy for Hepatitis C associated with an increased risk of liver cancer? The debate continues

Eight studies being presented at The International Liver Congress™ 2017 demonstrate contrasting evidence on the potential link between direct-acting antiviral treatment for Hepatitis C and liver cancer

April 20, 2017, Amsterdam, The Netherlands: According to data from eight studies being presented at The International Liver Congress™ 2017 in Amsterdam, The Netherlands, there remains continued debate on whether patients are at risk of developing liver cancer after achieving sustained virologic response (SVR) with a direct-acting antiviral (DAA) regimen for Hepatitis C virus (HCV). Investigators will present the results of their studies that show both sides of the argument – DAA therapy is associated with a higher risk of liver cancer compared with interferon-based therapy, versus there is no difference in liver cancer risk following cure with either therapy.

Whilst remarkable progress has been made in the development of successful antiviral therapies for HCV infection, some recent studies suggest that curing patients does not eliminate the risk of developing liver cancer. There also appears to be an unexpectedly high rate of liver cancer (also known as hepatocellular carcinoma [HCC]) recurrence in patients who previously had their tumour treated successfully and had received DAAs.

This claim was further supported by a Spanish study led by Dr Maria Reig and Dr Mariño, Hospital Clinic Barcelona, Spain in which patients with HCV and HCC who had previously been cured of HCC received DAA therapy. After a median 12.4 month follow-up, following treatment with DAAs, the rate of HCC coming back (recurrence) was 31.2% (24/77) and of those who received HCC treatment at recurrence, 30% (6/20) of patients presented progression in the immediate 6-month follow-up. This is an update of the study that will be published in the May 2017 issue of Seminars in Liver Disease, and is available here: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-0037-1601349.

“Our study offers further support to previous findings that there is an unexpected high recurrence rate of hepatocellular carcinoma associated with DAAs, and that this association may result in a more aggressive pattern of recurrence and faster tumour progression,” said Dr Maria Reig, Barcelona Clinic Liver Cancer Group, Hospital Clinic Barcelona, Spain, and lead author of the study. “These data indicate that there needs to be further research conducted in this area, clarifying the mechanism for the association between liver cancer recurrence and DAA therapy.”

Identifying those patients at risk of liver cancer is essential, a task that Dr Etienne Audureau, Public Health, Henri Mondor University Hospital, Créteil, France, and colleagues attempted to achieve by developing a prognostic tool for HCC. They found that in patients with severe scarring of the liver due to HCV (compensated cirrhosis), failure to achieve SVR was the most influential factor in predicting liver cancer. In addition, risk factors for liver cancer differ according to SVR status. The investigators recommend that in patients with compensated cirrhosis, eradication of HCV should be achieved before liver function is impaired and people who have achieved SVR should be monitored for liver cancer after 50 years of age.

The mechanisms behind the development of liver cancer following HCV cure are not yet understood. One group of investigators led by Prof Thomas Baumert, Inserm Institute for Viral and Liver Diseases, University of Strasbourg, France, aimed to investigate if HCV infections produce epigenetic and transcriptional changes that persist after the infection is cured, and whether these epigenetic changes drive liver disease and HCC following cure. They found that the epigenetic and transcriptional changes are only partially reversed by DAAs and persist after HCV cure, suggesting that these changes are a driver for liver cancer that develops after HCV infection has been cured. The investigators concluded that these findings open a new perspective to develop novel biomarkers to identify patients at high risk of HCC and provide an opportunity to develop urgently needed strategies for HCC prevention.

On the other side of the debate, a systematic review, meta-analyses, and meta-regression study, by Prof Gregory Dore and Dr Reem Waziry from The Kirby Institute, UNSW Sydney, and colleagues, found no evidence for higher risk of HCC occurrence or recurrence following DAA treatment, compared with interferon-based HCV therapy. A total of 41 studies, including 26 on HCC occurrence and 15 on HCC recurrence (in total, n=13,875 patients) were included. In studies assessing HCC occurrence, average follow up was shorter and average age was higher in DAA studies compared to interferon studies; incidence was lower with longer follow-up and younger age. In studies assessing HCC recurrence, average follow up was also shorter. Ultimately, in the meta-regression analysis, no evidence in favour of a differential HCC occurrence or recurrence was found between DAA and interferon regimens, after adjusting for study follow-up and age.

“Recent studies have reported contradicting evidence on risk of hepatocellular carcinoma following direct-acting antiviral therapy; our aim was to bring some clarity to this,” said Prof Gregory Dore, Kirby Institute and lead author of the study. “These data show the higher incidence of HCC observed following DAA therapy can be explained by the shorter duration of follow-up and older age of participants, rather than the DAA treatment regimen.”

A Scottish study, led by Dr Hamish Innes, School of Health and Life Sciences, Glasgow Caledonian University, Scotland, found that the risk of liver cancer following SVR was not associated with the use of DAAs, but baseline risk factors. Furthermore, risk of HCC development was similar in patients taking interferon-free regimens versus interferoncontaining regimens, following a multivariate adjustment (IRR: 0.96, p=0.929) and no significant differences in HCC risk were found when treatment regimen was defined in terms of DAA containing regimens versus DAA free regimens. These data indicate that rather than the treatment regimens themselves, it is the baseline risk factors that determine risk of hepatocellular carcinoma.

Another interesting study in Japanese patients with HCV genotype 1 infection, found a reduced incidence of liver cancer following achievement of SVR after 12 weeks of therapy with an interferon-free regimen (ledipasvir plus sofosbuvir) to a similar degree as that obtained with an interferon-containing regimen (simeprevir with peginterferon plus ribavirin). This study, which was conducted by Dr Masaaki Korenaga, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan, and colleagues, also found that unexpected development of liver cancer following SVR in patients without previous liver cancer could potentially be predicted by imaging procedures (computer tomography or enhanced magnetic resonance imaging).

Similarly, a Chinese study led by Dr George Lau, from the Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre, in Beijing, China, found no increase in the incidence of liver cancer in patients who achieved SVR12 with DAA compared to peginterferon plus ribavirin.

A Sicilian study conducted by Dr Vincenza Calvaruso, University of Palermo, Palermo, Italy, and colleagues, demonstrated that patients who achieved SVR with DAAs had a similar risk of developing liver cancer when compared to historical controls of patients with compensated cirrhosis who achieved SVR after interferon-based therapy. In addition, those who achieved SVR with DAAs had a lower risk of developing liver cancer than those patients whose HCV infection was not cured.

“The original observations made by researchers from the Barcelona Clinic Liver Cancer Group have sparked a huge number of studies aimed at verifying the potential association between DAA treatment and increased HCC recurrence after cure,” said Prof Francesco Negro, Divisions of Gastroenterology and Hepatology of Clinical Pathology, University Hospital of Geneva, and EASL Governing Board Member. “At this stage, there is no reason to alter treatment guidelines until the issue is definitively clarified. We cannot exclude, however, that we may have to revise post-SVR surveillance in some specific patient subgroups.”

- Ends -

About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2017 will take place from April 19 – 23, at the RAI Amsterdam, Amsterdam, The Netherlands.

Here is the response from EASL to the recent Cochrane review. http://www.journal-of-hepatology.eu/pb/assets/raw/Health%20Advance/journals/jhepat/CochraneEASLJMP003.pdf

EASL, the European Association for the Study of the Liver, one of the world leading associations of liver specialists, feels compelled to express its serious concerns after the recent publication of a Cochrane Group systematic review entitled “Direct acting antivirals for chronic hepatitis C” by Jakobsen et al. After reviewing 138 clinical trials, including 25,232 participants, the authors conclude that: “Overall, direct acting antivirals (DAAs) on the market or under development do not seem to have any effects on risk of serious adverse events. […] we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias, so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.”

The inability of the authors of the Cochrane review to determine a clinical benefit of DAA-based treatment of hepatitis C unfortunately reflects their flawed methodological approach and their ignorance of the natural history of hepatitis C virus (HCV) infection and associated systemic diseases. The review examines the intervention in a clinical vacuum that fails to accept that DAA treatment to attain an SVR is a pivotal outcome of treatment, and does not accept the likelihood that an SVR will reduce the risks of long-term outcomes of hepatitis C.

With this deduction comes responsibility. The uncertainty created by the illconceived Cochrane group’s conclusions and the attendant press publicity could grievously affect policy making, and constrain the gathering momentum for diagnosis, testing and linkage to care of individuals with hepatitis C. It will create dangerous confusion in the mind of patients treated or about to be treated and their families. The World Health Organization (WHO) has published an authoritative Global Hepatitis Report, expressing its alarm at the burden of disease, and has promulgated critical targets for global elimination of hepatitis C by 2030. In the absence of a prophylactic vaccine, the Cochrane review jeopardises treatment as a necessary intervention to reduce the global morbidity, mortality and prevalence of chronic hepatitis C.

The primary endpoint in DAA investigational drug development trials has been the sustained virological response (SVR), i.e. undetectable HCV RNA 12 or 24 weeks after completion of treatment, which corroborates permanent elimination of the viral infection. The Cochrane review evaluated the effect of DAA treatments on several outcome measures, including hepatitis C-related mortality, all-cause mortality, serious adverse events, no SVR and health-related quality of life (HRQOL). Most of their conclusions are flawed.

  1. The report from 32 trials including 7115 participants indicates that a total of 1180/1692 (69.7%) patients in the DAA groups and 915/5194 (17.6%) patients in the control group had “no SVR” during the observation period. This can only be an error as the authors deduce that meta-analysis showed that DAAs “seemed to reduce the risk of no SVR (risk ratio=0.44, p <0.00001) […]“.
  2. It is inappropriate to have pooled the data to include 57 trials that included drugs that have been withdrawn or discontinued. These are experimental drugs that have been discarded for lack of safety or inferior efficacy and that have been superseded by more effective and safer drugs, making the review dated and ignorant of current clinical decisions and guidelines in the context of a rapidly progressing field. Including treatments that are not or no longer used, and/or overly heterogeneous introduces a bias in the meta-analysis.
  3. From 43 trials involving 15,817 patients, the authors report serious adverse events (SAEs) in 2.7% of DAA-treated patients versus 5.5% in the control group during the observation period. They conclude that there is no firm evidence that DAAs reduce risk of SAEs. However, the terminology is clouded as the authors fail to clearly indicate whether they consider drug-related SAEs or clinical SAEs, i.e. clinical events resulting from the natural history of HCV infection which would happen months to years after the period of observation of the clinical trials.
  4. The HRQOL analysis has missed many recent studies. Several systematic reviews have been performed which have shown significant improvement in quality of life parameters with DAA therapy. The results show improvement over interferon and ribavirin-based treatments and are an encouraging aspect of an SVR with chronic hepatitis C, that further support the use of the SVR as surrogate. Very detailed and comprehensive analyses have been compiled before, during and after treatment objectively demonstrating improved patient-reported outcomes.
  5. The major weakness of the Cochrane review is that results are only assessed at “maximum follow-up”. These are of course short-term results for a disease with a long clinically latent period. A meta-analysis should only evaluate the primary endpoint selected by the clinical studies. The trials were not designed or powered to capture long-term outcomes such as hepatitis C-related morbidity or all-cause mortality, but to establish whether infection, reflected by persistent viremia, could be safely and effectively terminated.

The risk of clinical liver outcomes increases with aging and duration of disease. It is the result of chronic production of viral antigens during ongoing infection which incite host immune responses. The resulting hepatic inflammation in turn triggers fibrogenesis, the basis of liver disease progression towards aggravating fibrosis, cirrhosis and, ultimately, decompensated cirrhosis and hepatocellular carcinoma. The harmful effects of chronic hepatitis C take years to develop in patients that generally remain asymptomatic for long periods of time. Thus, although there is variation in rates of progression of fibrosis, early disease does not indemnify an individual from subsequent progressive disease, that can be accelerated by various cofactors and comorbidities. The authors of the Cochrane review have unfortunately not considered the possibility, the necessity and feasibility of arresting progression of early stage disease to more advanced fibrosis, cirrhosis, decompensated cirrhosis, or the ultimate development of HCC.

Achieving SVR, i.e. eliminating the infection, removes the trigger, thereby halting or considerably slowing the progression of liver disease. Terminating active infection also alters the natural history of a number of HCV-induced extrahepatic morbidities, such as diabetes and renal insufficiency. This has been clearly demonstrated by long-term follow-up studies in patients with chronic hepatitis C cured of their persistent infection during the interferon era. An SVR is associated with normalization of serum aminotransferases and improvement or disappearance of liver necroinflammation and fibrosis in patients without cirrhosis. Hepatic fibrosis generally regresses and the risk of complications such as hepatic failure and portal hypertension is reduced in patients with severe liver disease. Recent data showed that the risk of HCC and all-cause mortality is significantly reduced (although not eliminated to zero) in patients with cirrhosis who clear HCV compared to untreated patients and non-sustained virological responders. For the first time, DAAs have allowed patients with decompensated cirrhosis access to anti-HCV therapy, improving their liver function and reducing the indications for liver transplantation in a large proportion of cases, with a major impact on transplant programs already evident. Moreover, the possibility to treat patients after solid organ transplantation with high infection cure rates has opened the door to the use of HCVpositive grafts, increasing transplantation rates, reducing on-list mortality and containing healthcare costs for management of patients on the transplant waiting list.

National and international regulatory authorities have accepted the primary endpoint of an SVR and demonstrable safety as evidence for DAA licencing. Because the complications of chronic hepatitis C take years to occur, depending on the stage of liver disease, and clinical trials with new DAAs with SVR as main endpoint last only a few months, the benefits in terms of clinical outcomes of achieving an SVR cannot be measured in these trials. The Cochrane group’s conclusion is therefore illogical and inappropriate, as it fails to respect the methodology this organization has developed. The Cochrane review also ignores the opportunity of reducing the risk of transmission from viremic individuals, particularly in highrisk groups. Overall, the Cochrane review displays a lack of understanding of hepatitis C and drug development in the context of a transmissible infectious disease with a long natural history.

The Cochrane review authors’ conclusion that “randomised clinical trials assessing direct effects of DAA are needed” suggests an ethical anathema of leaving patients untreated to accrue increasing hepatic fibrosis, in the face of treatments that are likely to arrest viral replication in the overwhelming majority. This conclusion evokes memories of the infamous Tuskegee study conducted by the United States Public Health Service, in which patients with syphilis were left untreated to observe the natural history even after advent of and proven efficacy of penicillin. This unethical approach is unacceptable in a context where: (i) the HCV treatment landscape has markedly altered with the introduction of DAA-based regimens which in both clinical trials and real-world data have shown remarkable SVR (i.e. infection cure) rates in treatment-naïve and -experienced patients with or without cirrhosis across all genotypes; (ii) modelling has clearly demonstrated the benefits of DAA-based therapies in reducing long-term hepatitis C-related morbidity and mortality as compared to no treatment (individual benefit) and reducing HCV transmission (collective benefit). In summary, to arrive at such a flawed conclusion reflects the squandering of a vast amount of considerable time-consuming endeavour and significant public funding. The premise of the Cochrane review will be viewed as so egregiously mistaken that the conclusions will rightly be disregarded. As the findings do not assist or advance the field, they will not be pertinent to clinical decision making or guidelines.

EASL will continue to emphasize and reinforce the fight against HCV and to lend its support to the international efforts aimed at eliminating HCV, a major aetiology of severe liver and extra-hepatic diseases, complications and related mortality, by 2030. There is no precedent for a disease to be eliminated only 40 years after the discovery of its causal agent thus far. This chance cannot, and will not be missed.

This article was just published in the Lancet

The introduction of direct-acting antiviral (DAA) medicines in 2013 revolutionised the treatment of chronic hepatitis C virus (HCV) infection. The efficacy of DAA therapy is impressive—in many clinical trials HCV cannot be detected by sensitive laboratory assays in more than 90% of people who complete DAA therapy, and observational studies have documented similar results.1, 2 High efficacy combined with low rates of adverse events have led WHO to include DAAs in the WHO Model List of Essential Medicines.3 Several countries, including Australia, Georgia, Iceland, and Morocco, have started national DAA-based treatment programmes to eliminate HCV infection, and WHO has called for the expansion of HCV therapy with DAAs as part of its global hepatitis elimination strategy.4

HCV is an important contributor to global mortality, causing an estimated 399 000 deaths each year worldwide, and as HCV treatment expands, it is anticipated that mortality from HCV infection will decline.5 However, because the annual risk of death from HCV infection is low and the DAAs were introduced only recently, there are limited data on how these drugs affect mortality. Clinical trials that evaluate the efficacy of DAAs do not assess mortality as an outcome but rather a surrogate outcome called the sustained virological response (SVR). An SVR is defined as the absence of detectable HCV by nucleic acid testing of blood samples obtained 12–24 weeks after completion of HCV therapy. An SVR is deemed equivalent to a cure because once an SVR is achieved, it is maintained in more than 99% of patients, even after years of follow-up.6 Also, an SVR is associated with resolution of cirrhosis in about half of patients with cirrhosis followed-up clinical trials.7
However, documenting in a clinical trial that DAAs result in an SVR is not the same thing as showing that they reduce mortality or morbidity. A recent systematic review by Jakobsen and colleagues8 from the Cochrane Hepatobiliary Group sought evidence from clinical trials of HCV therapies to assess this issue. The authors reviewed randomised clinical trials that used SVR as the primary outcome in people receiving DAA therapy compared with those either not treated or treated with other regimens (primarily interferon-based therapy). Jakobsen and colleagues concluded that DAAs were effective in producing an SVR (relative risk 0·44, 95% CI 0·37–0·52); however, the analysis did not find a reduction in morbidity or mortality after DAA therapy. At first sight, this conclusion seems to contradict systematic reviews of observational data that show that people who have an SVR after treatment with interferon and ribavirin had a 50% (95% CI 37–67) reduction in overall mortality and 76% (95% CI 69–82) reduction in the incidence of hepatocellular carcinoma as compared with people who were treated but did not achieve an SVR.9, 10 The reduction in overall mortality was even greater (81% [95% CI 72–87]) when persons with an SVR were compared with those not treated.9 Other studies have shown improvements in extrahepatic manifestations of HCV infection and quality of life among people with an SVR after DAA treatment.11, 12 Data on the effect of DAA therapy are also beginning to be reported from national programmes that are scaling up HCV therapy. In England where HCV therapy increased by 48% in 2015, compared with 2014, there were reductions in the incidence of HCV-related cirrhosis (42%), liver transplantations (32%), and deaths (8%).13
Observational studies are biased towards showing an effect of treatment since treatment decisions are based on the likelihood of a successful outcome, and people achieving an SVR may be predisposed to a better outcome for reasons unrelated to the treatment. However, the magnitude and consistency of health benefits across studies and outcomes support the conclusion that HCV therapy resulting in an SVR substantially reduces mortality and morbidity.

How to explain these apparently contradictory results? An important difference between the studies reviewed by Jakobsen and colleagues is the duration of follow-up, which was short at an average of 34 weeks compared with an average of more than 5 years in the other reviews.9, 10 Simply put, the clinical trials included in the systematic review by Jakobsen and colleagues were not designed to answer the question posed by the authors about the effect of DAA treatment on morbidity or mortality. These studies generally followed up patients for only 24–48 weeks after the completion of DAA therapy, and the risk of HCV-related disease and death during such a short period is extremely low because the harmful effects of chronic HCV infection take years to develop. In fact, no morbidity was reported, and only 16 deaths occurred among the 2996 patients enrolled in all the DAA trials that were assessed by Jakobsen and colleagues. Thus, the statistical power to show a difference between the two groups is very low. In addition, the non-intervention groups in many of the studies included in Jakobsen and colleagues' systematic review did in fact receive HCV therapy, primarily an interferon-based regimen, which would minimise any mortality benefit of DAA therapy. Finally, Jakobsen and colleagues' study included early, less effective DAA regimens that were discontinued or withdrawn before marketing. They propose that, to resolve definitively whether DAA therapy reduces morbidity and mortality, randomised clinical trials with a non-treatment comparator group be done with clinically relevant outcomes such as death. Clearly, with the ready availability of safe and effective DAAs and ample evidence showing the health benefits of achieving SVR, such a study design is unethical and would be unacceptable to institutional review boards and harmful to patients' health. Several organisations, such as patients' groups and international hepatology associations, have expressed their concerns about the methods and conclusions of the Jakobsen review.14, 15, 16

People who are knowledgeable in the field of HCV therapy can readily ascertain the limitations of the approach taken in the systematic review by Jakobsen and colleagues and will be able to place their results in the proper context relative to other data that document the health benefits of DAA therapy. But for some patients, health-care providers, and decision makers who may be less knowledgeable about HCV therapy, this type of analysis, especially as reported in the mainstream media,17 could lead to conclusions that DAA therapy has no benefit, resulting in decisions to decline to prescribe or take DAA therapy or to decline to approve budgets for DAA treatment programmes, particularly in view of their expense. This would be a tragic outcome, as it would lead to preventable deaths. Public-health policy makers who must decide on budget allocations for HCV treatment cannot wait for perfect data on mortality endpoints, since the types of trials that would generate these data will never be done. Rather, they must assess available, albeit imperfect, data from observational studies and trials using surrogate outcomes that are reliably predictive of clinically important outcomes. Based on the fact that DAA therapy is safe and effective in achieving SVRs, that the SVRs are durable in most patients, that HCV-induced liver damage improves after SVR, and that observational data show a large reduction in morbidity and mortality, health-care decision makers and providers can take comfort that the evidence is strong in favour of treatment. A more definitive assessment of impact on morbidity and mortality will take time, but this should not be used as a reason for denying HCV therapy and delaying efforts to eliminate HCV infection.

How do I fix my insomnia

Saturday, 01 July 2017 00:55 Written by

About 1 in 5 patients taking Direct Acting Antivirals will get insomnia. Here is a post of mine from some years ago about how to manage it.

Insomnia is a common and often frustrating problem. Part of the reason it's frustrating is that, unless an accurate diagnosis of the root cause(s) is made, treatments tend to be temporary band aid solutions and rapidly lose their effectiveness.

Do you have an underlying medical problem?

There are a range of medical condition that can cause insomnia.

Chronic pain, sleep apnoea or a need to urinate frequently caused by an enlarged prostate gland can all cause insomnia.

Diseases like arthritis, cancer, heart failure, lung disease, gastroesophageal reflux disease (GERD), overactive thyroid, Parkinson's disease and Alzheimer's disease have all been implicated.

Mental health problems like stress, anxiety and depression can also cause problems.

Many of these issues are amenable to treatment, and by fixing the root cause, sleep patterns can return to normal.

Are your medications to blame?

  • Alpha-blockers
  • Beta-blockers
  • Steroids
  • SSRI antidepressants
  • ACE inhibitors
  • ARBs
  • Cholinesterase inhibitors
  • H1 antagonists
  • Glucosamine/chondroitin
  • Statins

Note that you should consult with your doctor before stopping any prescribed medications.

Are your daily habits contributing?

There are many habits and work patterns that promote poor sleep

  • Not enough light at midday and too much light (device screens) at night
  • Shift work - this scrambles your body clock (circadian rhythm)
  • Eating late in the evening
  • Fluids in the evening (we were all trained as children to wake up and not wet the bed)
  • Excess caffeine, nicotine and other stimulant (ie Red Bull) consumption
  • Using stimulants in the afternoon and evening
  • Not getting enough exercise
  • Too much alcohol - although alcohol is a sedative it prevents entry into deep sleep

Could your sleep hygiene be improved?

If you use your bedroom for other activities than sleep and sex you are missing the opportunity to program your thinking along the lines of go to bed, go to sleep.

You will sleep better if:

  • You have got a good dose of daylight during the day, and less light at night
  • Your bedroom is pitch black
  • Your bedroom is quiet
  • You bedroom is not too hot, not too cold
  • You have a comfortable mattress
  • You have a comfortable pillow - not too high or too low, too soft or too firm - get one that's just right (and remember they wear out over time)
  • You have enough blankets so you're not too hot when you go to bed, but also don't wake up freezing when it cools off in the early morning

What can my doctor do for me?

For a start, any doctor worth his/her salt can discuss everything with you and look for root causes. It's always best to fix the source(s) of problems.

A simple plan (from Dr Margaret Hardy)

  • Work out average amount of actual sleep per night from sleep diary
  • Choose a regular wake-up time
  • Set a regular bedtime by subtracting average sleeping hours from the planned wake-up time
  • Review at weekly intervals and, if tired, increase time in bed by going to bed 30 minutes earlier

Your doctor can also provide medications including:

  • Melatonin (which re-sysncs your body clock and is thus really good for shift work and jetlag
  • First generation sedating antihistamines (promethazine, doxylamine)
  • Benzodiazepines (temazepam, zopiclone, zolpidem and many others) which are good for short term (particularly stress related insomnia). Long term you become first tolerant (needing ever increasing doses) and then addicted (needed the medication or you won't be able to sleep)
  • Antidepressants like amitriptyline and mirtazipine which are used (usually in low doses) not to treat depression but for their common sedating side effect. Their advantage over benzodiazepines is that tolerance is far less of an issue, so they can be used longer term.Don't despair. Most people can get

Don't despair. Most people can get a far better nights sleep with a few simple changes.

Talk to your doctor, or see one of our expert GPs online from the convenience of home.

Dr James Freeman

Bad Science

Friday, 09 June 2017 01:34 Written by

Yesterday the Guardian published an article called 'Miracle' hepatitis C drugs costing £30k per patient 'may have no clinical effect'

https://www.theguardian.com/society/2017/jun/08/miracle-hepatitis-c-drugs-costing-30k-per-patient-may-have-no-clinical-effect

The problem with this sensationalist headline is that while it is reporting what was said by the Cochrane Collaboration what they looked at was trial specifically designed to test SVR rates, and not specifically designed to look at long-term outcomes.

Here is a commentary from Dr Andrew Hill and the study to which he refers which was presented at AASLD in 2015 and published in Clinical Infectious Diseases.

Total rubbish!  Here is our paper showing a really strong correlation between curing HCV and improved survival.
 
They only had 16 deaths included in the analysis!  
 
Please see the attached paper where we had much longer follow up and showed a strong effect of SVR on improved survival.  Our analysis included 2210 deaths - slightly more than the Cochrane study!

 

Reversal Of Liver Fibrosis - Then and Now

Tuesday, 02 May 2017 04:50 Written by

There is some really interesting stuff happening in the "reverse liver fibrosis" realm.

Here is state of the art in 2009 (great review of the mechanism) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702953/ where we had no clear candidates, and

Here is state of the art in 2015 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703795/ where we have literally hundreds of candidates (coffee and milk thistle (silymarin) and resveratrol are in there), and

Here is the state of the art in 2016 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754444/ in an article called Promising Therapy Candidates for Liver Fibrosis

I like this bit from the conclusion:

Since both animal experiments and clinical studies have revealed that liver fibrosis, even early cirrhosis, is reversible, treating patients by combined therapies on underline etiology and fibrosis simultaneously might expedite the regression of liver fibrosis and promote liver regeneration.

EASL 2017 Generics Results

Friday, 21 April 2017 22:17 Written by

Here is a copy of the generic hep c medication presentation given by Dr James Freeman at EASL 2017 today.

Mostly the presentation followed the slides.

The last words, with the last slide were "I want everyone to join the club, not the hep c buyers club, this club, the hep C cure club."

Click here to get the full slide set on generics presented at EASL 2017 in Amsterdam

A Brief History Of Sofosbuvir

Friday, 14 April 2017 08:33 Written by

“The Liver Meeting”, or AASLD 2011, was taking place at the great, glass-fronted Moscone West Convention Center in downtown San Francisco. Almost 9,000 people were there – family doctors, hepatologists, gastroenterologists, academics, drug salesmen, public health officials – all networking, trudging the escalators, wandering the beige exhibit halls, trying to stay on top of an avalanche of medical information. Across five days in early November, no fewer than 2,200 liver-related scientific abstracts were being presented, at sessions that ran from 6.30am until 9pm. Specialists in hepatitis C, an awkward, under-recognised health problem, were used to finding their way to the back rooms, the less-glamorous receptions.

Many felt it was time the disease moved up the agenda. Since it was identified in 1989, “Hep C” or “HCV” to those who work on it, has only confounded those who underestimate it. Transmitted through blood, the virus is now thought to infect around 2.5 per cent of the world’s population, or 170 million people. Of those, around a quarter will develop liver cirrhosis, or cancer, within a decade or two. In the UK, deaths from hepatitis C have trebled since 1996 and more than 200,000 people are infected. No one knows what to do about the coming demand for liver transplants. For the past decade at least, scientists have used phrases such as “gathering storm” and “silent epidemic” to try to bring attention to the subject.

There has also been a torrent of new data to keep up with. Despite its orphan status, the sheer numbers of people infected with hepatitis C have made it the subject of hundreds of millions of dollars of medical research – particularly by pharmaceutical companies, working on a new generation of drugs. And AASLD, as the world’s premier liver event, has become the occasion when information on those drugs – known as “direct-acting antivirals” – is often shared for the first time. In recent years, hepatitis C delegates had got used to turning up to must-see presentations that were filled way beyond capacity.

One look at the 2011 programme told conference-goers that a session on the Sunday afternoon – “HCV: Refining the Use of Direct-Acting Antivirals” – was going to be mobbed. Room 2001, on the second floor of the convention centre, only held about 400 people. Dr Ed Gane, a 51-year-old hepatologist and transplant specialist from New Zealand, who was to give the fourth of six presentations in the session, arrived about 10 minutes before it was due to begin. “It was packed to the gunwales,” he told me. Conference staff began setting up a video link to adjoining rooms to cope with the spillover.

The cognoscenti were there to hear Gane. An unshowy, respected doctor, he had been working on hepatitis C since the early 1990s, and for the past year, had been carrying out a clinical trial of a particularly promising new drug developed by a small American pharmaceutical company called Pharmasset. The drug was known by its laboratory name, “PSI-7977”, and today, Gane was to give an update on the trial, called ELECTRON.

Read The Full Article

The Story Of Generics Hits The Lancet

Friday, 31 March 2017 04:32 Written by

An article with the title: Importation of generic hepatitis C therapies: bridging the gap between price and access in high-income countries just made it into the Lancet print edition:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)32051-7/fulltext

There is a PDF of it here

Liver Iternational - Generic Hepatitis C Medication

This article about the rationale for using generic hepatitis C medication has just been published in Liver International in their section "Debates in Hepatology".

James A. D. Freeman1 and Andrew Hill2

1 GP2U Telehealth, Hobart, Tas., Australia
2 St Stephens AIDS Centre, Chelsea and Westminster Hospital, London, UK

Liver Int. 2016; 36: 929–932. DOI: 10.1111/liv.13157

Abstract

Hepatitis C, hepatitis B, HIV, TB and malaria are the five major causes of infectious disease death worldwide. In a breakthrough that rivals the invention of penicillin, drugs that cure hepatitis C, with minimal side effects and high success rates, have reached the market, but, in what must be one of the greatest tragedies of modern times, these life-saving medications are not being deployed on a mass scale. Pharmaceutical patents are gifted to private corporations by governments for the dual purposes of protecting R&D expenditure and encouraging innovation. Unfortunately the monopoly pricing power these patents provision currently lacks adequate checks and balances, is open to abuse, and is quite clearly being abused. The sort of legislative changes required to deliver on the original goals of pharmaceutical patents will take years or even decades to eventuate. Parallel importation of generic medication offers hope to the millions of patients with HCV unable to afford access to vastly overpriced originator medications. Doctors prescribing and monitoring patients taking generics can take comfort from the fact that the REDEMPTION trial results show, like the HIV generics that came before them, that HCV generics deliver robust clinical results.

Read the full article at: http://onlinelibrary.wiley.com/doi/10.1111/liv.13157/full 

To find out more about generic hepatitis C medication please visit our forum where you can read the stories of patient successfully accessing and treating their hepatitis C with affordable generic medication.

According to a report on Tuesday, said Delaware State would embark on a new Medicaid policy program all in an attempt to treat hepatitis C patients.

Added pressure will not be enough

hepatitis c delaware
Ever since Obama Administration and lawsuits assumed office, most States are considered to be under pressure from the Delaware's case. For instance, Harvard Law School's Center for Health Law and Policy Innovation had threatened litigation to abandon money in response to policies that limits treatment of sick patients with expensive new medications. 

However, many US citizens are waiting for their respective State to come up with a legislation that would cover the high costs of Hepatitis C treatment. Delaware is not an insulated case; but there is a long way from legislation to actual treatment. Hepatitis C patients are advised to seek treatment as quickly as possible in order to prevent further liver decay - and by far quickest method of getting Hepatitis C medicines with a considerable discount is by using Fix Hep C Buyers Club

Hepatitis C patients can talk with Dr. Freeman about procuring the following medicines:
  • sofosbuvir + ledipasvir (Harvoni®)
  • sofosbuvir (Sovaldi®)
  • daclatasvir (Daklinza®)
  • ribavirin (Ibavyr®)
Here is Dr. Freeman's contact where you can inquire about your treatment options and how to import Hepatitis C medicines for low cost. 

Hepatitis C overview

Over three million Americans are likely to be infected with hepatitis C, a bloodborne virus spread viа blood аnd bоdу-fluid contact ѕuсh аѕ blood, ѕеmеn, bоdу fluid, IV drug abusers ѕhаring needles or ѕоmеоnе uѕing tainted needles. Hераtitiѕ C uѕеd tо be thе mоѕt соmmоn tуре оf hераtitiѕ аcquirеd thrоugh blood trаnѕfuѕiоnѕ until a tеѕt fоr it bесаmе аvаilаblе in thе 1980ѕ.

Hераtitiѕ C саuѕеѕ inflаmmаtiоn оf the liver rеѕulting in liver damage that саn lead tо cancer. It аlѕо соmmоnlу lеаdѕ tо chronic livеr inflаmmаtiоn аnd ѕlоwlу dаmаgеѕthе livеr оvеr a lоng period оf time bеfоrе lеаding tо cirrhosis оf thе liver, that means scar tiѕѕuе rерlасing normal, healthy tiѕѕuе in rеѕult оf blocking thе flоw оf blood thrоugh the livеr and preventing it from frоm working аѕ it ѕhоuld.

Delaware Hepatitis C coverage

The Delaware State issue can be likened to that of New Jersey in that evidence is still required prior to liver damage approval treatment.

The new initiative policy permits a specific severity restrictions by July 1 and holds a requirement for patients on drugs abuse, thus bring in line with medical standard recommended for treatment and prevention of such infectious diseases.

Other changes will occur, for all hepatitis C-infected patients on Medicaid in Delaware who are eligible. The treatment new legislation takes effect on Jan. 1, 2018. The change as announced on Tuesday at Harvard was confirmed by a spokeswoman from Delaware Department of Health and Human Services that the State will definitely change its policy.

 This initiative policy changes has already been embarked by other states. As it stands, an advisory committee set in Pennsylvania recommended that the state Medicaid initiative policy should treat all patients in that regard; a decision yet to be confirmed.

For all other patients, it is best to seek help using Fix Hep C Buyers Club. Contact us today and get your medications within a month.
Приветствуем, всех, кто затронут вопросами хронических гепатитов,

Мы рады представить некоммерческий проект «ГЕПАТИТКА», созданный группой активистов для поддержки, помощи и общения людей, затронутых вирусными гепатитами B, C и D.

Начало этого проекта было положено в марте 2012 года пациентом из Москвы во время того, как он проходил курс лечения гепатита С пегилированнымиинтерферонами и рибавирином. Чтобы облегчить проживание сложных побочных эффектов, связанных с лечением, молодой человек начал взаимодействовать с людьми, затронутыми гепатитом С. Он делился своим опытом, рассказывал, как передается гепатит С, мотивировал лечиться, а не ждать развития фиброза, пояснял, как можно поддержать человека на лечении, организовывал совместное времяпровождение и он-лайн взаимодействие людей, связанных с гепатитом С.  Вокруг него образовывалось сообщество людей, связанных с гепатитом С. Сообщество разрасталось, вышло за пределы Москвы и в октябре 2013 года его товарищ из Минска, замотивированный на лечение гепатита С, создал группу в социальной сети фейсбук. Этой группе далось запоминающееся название – ГЕПАТИТКА.

В 2015 году проект переформатируется, благодаря присоединению к работе и разносторонней поддержке коллег из ITPCru. Весной 2015 года в группе ГЕПАТИТКА в фейсбуке начала появляться информация о прорыве в лечении хронического гепатита С в виде появления на рынке препаратов для лечения гепатита С с принципиально новым принципом действия, с почти 100% эффективностью, легких по переносимости и с сокращенным сроком лечения.  ГЕПАТИТКА была одним из первых ресурсов, где появились новости по доступу к лечению ВГС в мире новыми безинтерфероновыми схемами, где были опубликованы перечни доступных безинтерфероновых генерических препаратов для лечения ВГС с указанием цен  и производителей. Ресурс подкреплял новостную информацию о препаратах переводенными на русский язык международными клиническими рекомендациями по лечению новыми схемами, а также результаты КИ по ним. При этом составом координатором ГЕПАТИТКИ было принято решение поддерживать исключительно традиционные мировые методы диагностики и лечения. Благодаря выкладываемой информации, постоянной работе с пациенстким сообществом и опыту первопроходцев, кто уже не мог откладывать лечение и воспользовался новыми препаратами, появилось много информации о ходе лечения новыми препаратами в режиме он-лайн, и как следствие, много возможностей расширения доступа к лечению гепатита С для всех нуждающихся и очевидная необходимость развития проекта ГЕПАТИТКА в разных направлениях.

На июнь 2016 года проект представлен в следующих ресурсах:

- закрытая группа фейсбук (3477 участников): https://www.facebook.com/groups/NAHCV/

 - закрытая группа в ВКОНТАКТЕ (475 участников):  https://vk.com/gepatitkaru 

- сайт http://gepatitka.ru/, где доступен пациентский форум, а также последние мировые рекомендации по лечению ВГС и бесплатное медицинское консультирование по вопросам хронических гепатитов в режиме он-лайн.

На сегодня проект ГЕПАТИТКА координируется небольшой группой активистов из Москвы, Санкт-Петербурга и Минска. В планах стоит расширение развития в регионах ВЕЦА, в проекте на ежедневной основе задействованы активисты из РФ, Украины и Латвии.  В проект вовлечены два медицинских специалиста, практикующих гепатолога, из Германии и России.

Добро пожаловать всем, кто затронут вопросами гепатитов на площадки проекта ГЕПАТИТКА. Вы сможете найти много полезной информации и общения там.

------

Dear all, especially Russian speaking audience,

We are pleased to present a non-profit project "GEPATITKA" for the Russian audience. Project was created by a group of activists to support and to coordinate communication between people, affected by viral hepatitis B, C and D.

Project started in March 2012 while a patient from Moscow (Russian Federation) was undergoing pegylated interferon and ribavirin treatment for hepatitis C. In order to handle tough side effects and not to stay alone with his condition, he started to share his experience with others, started to learn more about HCV and to share his knowledge. Very soon a community of patients grew around him. He treated his HCV and continued his activities to help others. He motivated his friend from Belarus to start treatment as well and in October 2013 the project appeared on-line, on FACEBOOK, and got it name – GEPATITKA (Gepatit means Hepatitis in Russian). 

In 2015 the project GEPATITKA was reformatted (got a new structure), due to the joining of ITPCru. GEPATITKA started to spread out information about new landscapes in HCV treatment, about the DAA appearance in the world with almost 100% efficiency, easy portability and a reduced period of treatment. GEPATITKA was one of the first resources in the EECA region, where information about PEG-IFN-free regimens was published and lists with DAA generics with prices and producers appeared. Project supports its publications with the international clinical guidelines, and only traditional methods of HCV diagnosis and treatment. Due to the strong informational work and very attentive and intense approach to the patient’s community project GEPATITKA became very popular in the Russian speaking countries, especially in Russia, Belarus and Ukraine.

In June 2016 GEPATITKA project is presented in the following resources (only in Russian language):

- Private group on Facebook (more than 3500 participants): https://www.facebook.com/groups/NAHCV/

- Private group in a Russian social network VKontakte (around 500 participants): https://vk.com/gepatitkaru

- at the web site GEPATITKA: http://gepatitka.ru/
This web site provides not only the latest world updates for HCV treatment and free medical consultations for chronic hepatitis in the online mode, but also a platform for the patient’s forum.

Today GEPATITKA project is being coordinated by a small group of activists from Moscow, Saint Petersburg and Minsk (Belarus). They plan to expand in the EECA regions. A number of volunteers, who are affected by hepatitis, from Russia, Ukraine and Latvia are involved in this project on a daily basis. Two medical specialists, hepatologists from Germany and Russia answer questions on the web site free of charge on the daily basis.

Resources of GEPATITKA are very friendly and patient - oriented and warmly welcomes everyone who is affected by hepatits.
In the world of Hepatitis C, the chances of getting the medical insurance to cover the high costs of your drugs comes down to a fibrosis score of an individual patient. In the US for example, Medicaid providers will in many cases cover the $94,500 Hepatitis C drug Harvoni costs only to the sickest patients, determined primarily by the measure of liver scarring or fibrosis score.

Efforts are being done to expand the insurance coverage to all Hepatitis C patients but it is an uphill battle. It is our hope that in some years, insurance companies will include Hepatitis C coverage in the majority of healthcare plans; however, Hepatitis C patients can't afford to wait for years on end to get the medicines.

FixHepC Buyers Club works much quicker. We can supply every Hepatitis C patients, regardless of fibrosis score, with an affordable Hepatitis C drugs (sofosbuvir, ledipasvir, daclatasvir, ribavirin). For everybody in need of Hepatitis C drugs, please do contact Dr. Freeman via email or phone and you will be able to discuss the proper course of treatment and how to obtain the medications.

Washington Judge Orders Medicaid to Save All Hepatitis C Patients


A federal judge has ordered Washington state’s Medicaid provider to cover expensive hepatitis C drugs for all patients with the liver-destroying disease, not just those who are sickest. Up till now, the coverage included only the patients with the most problematic fibrosis score. This has left thousands of patients in Washington alone without the access to the medications; not many could fetch up more than $80,000 for the medicines. 

U.S. District Court Judge John C. Coughenour granted a preliminary injunction Friday that forces the state Health Care Authority (HCA) to halt a 2015 policy that restricted access to the drugs based on a fibrosis score, a measure of liver scarring.

Fibrosis Score

Hepatitis C drugs are expensive; so much so that many of health insurance companies would go down if they had to cover the expenses of all Hepatitis C patients. 

This is why a sieve was created to determine which Hepatitis C patients need the medicines the most. The state of liver plays a key role in this selection process. Fibrosis score is used to get a basic understanding in how good a shape a liver is, and the decision process for many health insurance companies is as follows:
  • 'Good' Fibrosis Score - No insurance coverage of Hepatitis C drugs
  • 'Bad Enough' Fibrosis Score - Insurance covers Hepatitis C drugs
This system is very problematic because the insurance will only cover Hepatitis C expenses for the sickest of patients. Everybody else with Hepatitis C has to wait for his or her liver to be ruined enough (according to fibrosis score) to qualify for Hepatitis C drugs coverage.

FixHepC Buyers Club - We Cure Everybody Regardless of Fibrosis Score

We all know that Hepatitis C is a deadly disease if left untreated. Why should only patients with a bad fibrosis score get the medical coverage? This is exactly what Washington Judge  John C. Coughenour pointed out. Eventually, even people with the best fibrosis score will have their liver damaged beyond repair and looking for help then will be too late.

FixHepC has organized itself as a safe establishment to procure the necessary Hepatitis C medications to every patients.
  • 'Bad' Fibrosis Score - We will help you get the medications (patients with bad fibrosis score need it the most)
  • 'Good' Fibrosis Score - We will help you get the medications (patients with good fibrosis score will have their liver damaged in years to come - the time to act is now!)
For further instructions on how to get the low-priced Hepatitis C medications, please contact Dr. James Freeman here.

The Washington Case

The injunction was a response to a class-action lawsuit filed in February on behalf of two clients of Apple Health — and nearly 28,000 other Medicaid enrollees with hepatitis C.

The two patients, a 53-year-old Seattle woman and a 47-year-old Lakewood man, were prescribed the drug Harvoni to treat their hepatitis C infections. But they were denied the drug, which costs about $95,000 for a 12-week treatment, because of its cost, the complaint said.

The injunction orders HCA to begin covering Harvoni “without regard to fibrosis score.” The judge ruled that the agency’s policy was not consistent with existing state and federal Medicaid requirements that drugs be dispensed based on medical need.

“For people who have been living with this disease and feeling like there’s no hope if they can’t get this cure, this is life-changing,” said Ele Hamburger, a lawyer with the firm Sirianni, Youtz, Spoonemore and Hamburger, which filed the lawsuit. Co-filers included Columbia Legal Services and the Center for Health Law and Policy Innovation at Harvard Law School.

It’s not clear how soon Medicaid patients with hepatitis C may begin filling prescriptions for Harvoni and other direct-acting antiviral drugs. The ruling orders all parties to report back within 60 days.

HCA officials are reviewing the injunction, a spokeswoman said. But the state Medicaid director, MaryAnne Lindeblad, estimated in a letter to the U.S. Senate last fall that paying for hepatitis C treatment for all Medicaid clients in Washington would be three times the agency’s current $1 billion drug budget.

Medical guidelines had previously supported limiting the drugs to the sickest patients, but that changed last year. Experts in liver treatment and infectious disease now agree that drugs such as Harvoni should be used to treat all patients, including those with mild disease.

Time to Act is Now

Waiting for your liver to have a bad enough fibrosis score for insurance company to cover Hepatitis C costs is literally playing with your own life.

We can help you to get the Hepatitis C medications within a month. Send us an email and we will help you get over Hepatitis C once and for all.
 

Hardev Karar we salute you. R.E.S.P.E.C.T

Wednesday, 11 May 2016 11:41 Written by
So now it's common knowledge that the Indian patent office has approved Gilead's sofosbuvir patent but....

What Happened to the Indian Official that Rejected the US Drug Company Gilead’s Patent Application in 2015?

It appears that being a man of honour is less valued than it should be.

http://www.caravanmagazine.in/vantage/indian-official-rejected-gilead-patent-forced-out

Hardev Karar, I salute you as a man of honour and integrity.

Dr James Freeman

 

End of Hepatitis C Tourism?

For more than a year, Hepatitis C patients who could not afford the high price tag of the novel Hepatitis C drugs in their respective countries, could go to India and buy the medicines they needed to get well for about $2,000. This window that cured thousands and thousands of patients is about to close, as the result of Indian patent office ruling on drug Sovaldi (400mg sofosbuvir).

Gilead Sciences, the pharmaceutical company that makes Sovaldi, failed to show the inventiveness and novelty sufficient to grant a patent on Sovaldi. Since they did not wish to lose such a big market as India, they gave licences to 11 generic manufacturers in India to produce and distribute the low-cost sofosbuvir pills as their plan B (getting a patent being a plan A).

According to Reuters, Gilead appealed against the ruling that refrained Indian patent office from giving them a patent on sofosbuvir molecule. In a dramatic change of heart, Indian patent office just gave Gilead what they wanted all along - a patent. With the plan A in play now, Gilead might choose and forgo plan B - this would mean that there would be no more low-cost sofosbuvir pills to import from India and would leave millions to choose between fetching out more than 80,000$ for the original medicine, or face the lethal consequences of untreated Hepatitis C.

Fix Hep C Buyers Club supply of Hep C drugs is not affected

The Fix Hep C Buyers Club remains one of the strongest providers of low-cost Hepatitis C medicines. Since sofosbuvir the buyers club provider is supplied from China, not India, the supply chain will not be affected and every Hepatitis C patient can seek help they need by contacting us (click here).

Why did the Indian patent office change its mind?

In direct contradiction to its earlier order, the Controller General of Patents, Designs and Trademark granted American pharmaceutical company Gilead Sciences the patent for the blockbuster Hepatitis C drug Sofosbuvir (brand name Sovaldi) in India. An application for the same patent was first rejected in January 2015 as lacking inventiveness and novelty.

On Monday, however, the patent office dismissed all pre-grant oppositions and stated that it found, “claimed compounds are novel, inventive and patentable under Patents Act.” The decision is a major blow to the access to drug movement, said Leena Menghaney, South Asia head of Médecins Sans Frontières (MSF). “There has been excessive pressure building up on the Indian government to dilute the independent functioning of the patent office to ensure that patent claims are granted far more easily to U.S. firms. In the process, the patent office has completely ignored recent proceedings in the U.S. against Gilead regarding the same application which have been found to infringe two of Merck’s patents, clearly defeating Gilead’s claim that its application on the drug was novel,” added Ms Menghaney.

How obtaining a patent works 
india patent
 
“These are very scary times for the patient communities globally who rely on affordable generic medicines coming from India. The government’s “Make in India” campaign seems to be only for foreign companies and not for Indian generic industry which has been the lifeline for people across the world,” said Loon Gangte with the Delhi Network of Positive People

Gilead, in a statement, welcomed the move, but said it will have no impact on availability of the compound, which is already licensed to 11 generic manufacturers in India for distribution in 101 developing countries.

Sofosbuvir patent issue goes beyond patent office

Another key application on sofosbuvir is pending before the Kolkata patent office and several oppositions to its grant have been filed by patient and public interest groups. Stating that the case had been decided outside the merit of the technical and legal issues, Tahir Amin Co-Founder and Director of Intellectual Property Initiative for Medicines, Access & Knowledge (I-MAK) said that the organisation would appeal against the decision. “The Indian patent office has had to deal with a lot of external influences around this case, especially since the initial decision last year. Clearly the decision has been taken outside the realm of the patent office. The decision has not been reasoned properly and there are a lot of discrepancies. The interpretation of the law as it is intended has not been applied and we will be appealing against it.”

Get your Hepatitis C medicines today at Fix Hep C Buyers Club

Pharmaceutical companies are trying ever harder to restrain the production of low-cost Hepatitis C medicines on all fronts. For them, a Hepatitis C patient is worth $80,000 or more. For us at Fix Hep C Buyers Club, Hepatitis C patient is worth saving because we consider it morally a right thing to do; this is why we have obtained a legal and safe way for Hepatitis C patients to obtain the medicines they need for less than $2,000. Please do contact us with the nature of your disease and Dr. Freeman will advise you on the best way of treatment, and what is even more important, we will deliver the treatment to your doorstep as soon as possible.

According to the Center for Disease Control and Prevention (CDC), Hepatitis C is currently the most deadly infectious disease in the US. The findings are based on new government data about Hepatitis C related deaths in 2014. What is even more concerning is that in 2014 Hepatitis C accounted for more deaths than 60 other infectious diseases, including tuberculosis, HIV/AIDS and pneumococcal disease.

The irony of the problem is that in 2013 we have discovered a wonder drug to cure Hepatitis C patients, with about 95% cure rate. However, in 2014 we were faced with an all-time high death cases due to Hepatitis C virus. How can this be?

"Not everyone is getting tested and diagnosed, people don't get referred to care as fully as they should, and then they are not being placed on treatment," said Dr. John Ward, director of CDC's division of viral hepatitis.
hiv and hcv

Report on 2014 Hepatitis C related deaths by CDC

One of the reasons may lie in better reporting. CDC gathers information about Hepatitis C related deaths via computerised reporting system; in 2014, 40 states reported their Hepatitis B cases and 37 states disclosed statistical number about their Hepatitis C patients. 

According to CDC report, the reported cases of acute Hepatitis C virus infection increased dramatically. While during the years 2006-2010 there were less than 1000 reported cases of infection per year, the number quickly rose to above 2000 cases per year in 2013 and 2014. That is more than 100% increase in less than 5 years. No doubt better reporting is in part responsible for the statistical increase; albeit that does not diminish the ever rising increase in HCV incidence.

New US Hepatitis C Numbers

Up till the CDC report that came out on 4th of May 2016, the rough consensus on the number of HCV infected patients in the US was about 3.2 million. Now the number is more likely closer to 3.5 million, a nearly 10% increase in all Hepatitis C patients. What is more, the epidemiologic studies show that at least 4.6 million people in the US are HCV-positive. All of these people do not suffer from Hepatitis C; however, a very large majority has high probability of suffering the consequences of Hepatitis C.

Who are the new Hepatitis C patients?

Using the statistical data from all the reporting states, CDC pointed out the demographics of people who's incidence of getting Hepatitis C is increasing the most. Here is a profile of a person now most likely to be infected by HCV:
  • Young white persons
  • Non-urban area residents (especially in Midwestern and Eastern states)
  • History of injectable drugs use
  • Use of opioid agonists such as oxycodone
CDC does admit that the higher numbers in areas such as Florida, Massachusetts and New York can be a result of increased surveillance as a result of their funding. However, the increase in other states was affected by better reporting in a lesser way.

Overall, factoring in the under-reporting and under-ascertainment, CDC estimates more than 30,000 people got infected with HCV in 2014 alone.

Hepatitis C related deaths

An average age of Hepatitis C patient that succumbs to the disease is 59 years. What is concerning is that there has been a drastic increase in Hepatitis C related deaths in adults aged 55-64 years old.

2007 marks the year when Hepatitis C related deaths (15,106) exceeded the number of HIV/AIDS related deaths (12,734). From that point on, we see Hepatitis C deaths gaining momentum while HIV/AIDS patients are doing better than before. 

In 2014, almost 20,000 US citizens died from Hepatitis C; more than half of those were in the 55-64 years range. Baby boomers -- those born from 1945 to 1965 -- carry the greatest burden associated with the disease, as many have been unknowingly living with it for years.

You can access the full commentary on CDC report on Hepatitis C here

 
Meet Steve.

Steve is 58 years old and had Hepatitis C for 10 years. With all the rumors about these new direct acting antivirals (DAA) treatment being so successful, he and his doctor make a decision to start sofosbuvir-based treatment of his genotype 1 Hepatitis C condition.

During the treatment Steve's well-being in being improved and after 3 months the tests show he is Hepatitis C free. He is giddy and excited about it like a little child and tells everybody that a decade-long fight with Hepatitis C is finally over and he had won. He even throws a party to commemorate the moment.
hepatitis c virus

Now meet SVR. It is a clinical parameter that stopped Steve's breath. 4 weeks after treatment the same doctor that said he is cured of Hepatitis C, says that he is in fact not free of Hepatitis C at all. His viral load, which was zero when he finished the full treatment, was now up and rising. How can this be?

This is a story some Hepatitis C patients go through. After being told there is no HCV detected in their blood after treatment, the standard check up shows signs of Hepatitis C coming back, and the doctors are saying something in the terms that the measure of true cure rate of the medications is SVR. SVR4, SVR8, SVR12 and so on. Many patients are a bit confused when it comes to grasping the difference between successful treatment and SVR parameter. This is why today we will explain what does SVR mean; knowing this will make it easier for patients to better understand Hepatitis C and how it may 'come back' shortly after finalized treatment.

Difference between cure rate at the end of the treatment and 4-24 weeks after the treatment

After every treatment, especially as costly as above $80,000 Hepatitis C treatment (for the low-cost medications you can contact us), there is one thing every patient wants to hear - 'You are cured.'
In the case of Hepatitis C, the majority of people hear those exact words. In fact, even when the above 95% cure rate DAA treatment was not available and the golden standard of treatment was interferon, many patients heard those words.

Hepatitis C virus comes back.

In actuality, the SVR and cure rate have a lot to do with our method of detecting the presence of HCV. 
During and after treatment, the HCV RNA viral load is measured - with the treatment working successfully, the viral load goes to zero and we interpret this result as being cured. In fact, however, having zero viral load only means that the current method of detection that works by identifying HCV's genetic material - RNA in viruses - has not detected any HCV RNA. To be even more correct, the levels of genetic RNA material of HCV in the blood was below the limit of detection of the method for measuring HCV presence.

Cure rate at the end of treatment

During the sofosbuvir-based treatment, patients take pills orally, the therapeutic DAA are absorbed into the bloodstream and from there they go wherever the blood goes and even beyond - into liver cells for example. However, the majority of the medication is circulating in the blood and it is in the blood that they have the greatest effect. At the end of the treatment, we look at blood for HCV, and upon finding none of it, we might say there is no detectable Hepatitis C.

However, HCV can be, for the lack of a better word, sneaky. In some cases, it 'hides' from the bloodstream only to be detected at a later time when it multiplies enough to start slipping into the bloodstream. 

The great thing about the novel DAA treatment is that it 'finds' every virus there is and helps destroy it. In the case of older interferon treatment, it was very successful at eliminating the HCV in blood stream but the recurrence rate was high. 12 weeks after treatment, SVR12 or sustain virological release 12 weeks after treatment, was not 100%. It was closer to 50%; this is why we say that interferon successfully cures Hepatitis C only in about 50% of cases.

The DAA-based therapeutics such as sofosbuvir, ledipasvir, ribavirin and daclatasvir always include two distinct therapeutic molecules to scoop out all HCV. Let's say that sofosbuvir reaches and helps destroy 99% of the virus, it's counter part molecule - let's say daclatasvir - takes care of the remaining 1%. If that 1% would be allowed to survive the treatment, it wouldn't be detectable in the bloodstream right after treatment; however, after some weeks, it would multiply enough to be detectable. Detecting it would be a medical confirmation of Hepatitis C recurrence. 

Luckily, with the new treatment, the number of patients who have zero load immediately after treatment and who retain this zero load even after 4 and 12 weeks, is very great. We talk about above 90% SVR4 and SVR12.

SVR4, SVR12 and SVR 24

Generally speaking, the likelihood of Hepatitis C coming back a long time after treatment (SVR24) is extremely low (1%). The majority of patients where recurrence is happening is discovered 4 weeks after the end of treatment (SVR4). Here is a graph from Dr. Freeman's presentation, depicting the percentage of cure rate immediately after treatment versus 4 weeks after treatment.



As we can see from the graph, immediately after treatment (EOT) every patient except for 1 was 'cured'. However, the more realistic cure rate is depicted by SVR4 - this means the percentage of patients who were free of Hepatitis C 4 weeks after treatment. As seen from the results, the blood samples of a total of 8 patients have been positive on HCV RNA 4 weeks after treatment. These are the unfortunate, Steve's which brought the cure rate down to 94.4%. 

Why is SVR important?

Obviously the higher SVR4 or SVR12 a certain cure has, the better it is. Nonetheless, high SVR or high cure rate comes with some perks as well.

According to studies by Pearlman and Traub from Center for Hepatitis C, SVR-achieving patients saw a 'histologic regression of both necroinflammation and fibrosis '; this means the liver responded positively to being cured. What is more, patients with SVR were found to have less liver-related complications such as hepatocellular carcinoma, which translates to less liver-related deaths. According to an up-to-date statistics, about 500,000 people die from Hepatitis C or Hepatitis C related diseases annually.

Another interesting discovery by Pearlman and Traub is that successfully getting rid of HCV, which is associated with the increased insulin resistance, decreases the chances of getting Type II diabetes. This is also why HCV should be treated as soon as possible; the occurrence of other disease and liver damage can be reduced.

 
As a part of the effort to solve the unavailability of modern Hepatitis C drugs, REDEMPTION-1 clinical trials were conducted in order to determine the safety and efficacy of generic direct acting antivirals (DAA) to treat Hepatitis C. The trials were lead by Dr. James Freeman of FixHepC Buyers Club who gave a presentation on the outcomes of the trial at the most important event for liver-based diseases - The International Liver Congress 2016; an event gathering over 10,000 medical and scientific experts from all over the world was held in Barcelona, Spain.

Here below is Dr. Freeman's presentation with added explanations. You can download full version of REDEMPTION-1 clinical trials below (see attachment).
redemption-1 clinical trials

The True Scope of Hepatitis C

As Dr. Freeman neatly put it, the discovery of the modern Hepatitis C drugs that consist of DAA rivals the invention of penicillin by Alexander Fleming in 1928. What is interesting in this analogy, is that penicillin became widely used only in 1942 during the WWII. The DAA treatment is currently available to anyone - with deep enough pocket. Out of estimated 150 million Hepatitis C patients, only 500,000 are treated with the DAA annually. That is less than 1%.

Of the Top 5 major causes for infectious disease, Hepatitis C just might be the one that is known the least. However, with the revolutionary DAA treatment making headlines, Hepatitis C awareness is slowly building momentum and the true scope of problems connected with Hepatitis C are becoming more obvious every day; as is the problem of the high prices of branded Hepatitis C treatments.

Top 5 Major Causes of Infectious Diseases:
  • HIV/AIDS
  • Hepatitis B Virus (HBV)
  • Tuberculosis
  • Malaria
  • Hepatitis C Virus (HCV)

We have had effective treatments for all of these diseases except Hepatitis C for more than a decade. It was in late 2013 that first DAA molecule called sofosbuvir was launched which should in effect greatly improve the world's Hepatitis C statistics by curing Hepatitis C patients. After all, the new Hepatitis C treatments have a cure rate of about 95% with minimal side effects.

Here are some up-to-date statistics on Hepatitis C as presented by Dr. Freeman:
  • We have 150 million patients infected with Hepatitis C virus
  • We have about 500,000 death connected with Hepatitis C and Hepatitis C related disease
  • Even with the effective DAA treatment discovered, we treat only 500,000 patients per year
If you give yourself a moment for these numbers to sink in, the obvious question is:

"If we have 150 million patients, why do we treat only 0.5 million of them? Especially with another 0.5 million patients dying every year."

The answer is pretty obvious as well.

How Big Pharma prices Hepatitis C medicines

The problem is the high cost of treatment.
Big Pharma is apt to increase prices of innovative drugs; nonetheless, the Hepatitis C treatment area is another problem altogether because of the very extremes Big Pharma went to price Hepatitis C treatments that are of questionable innovation and are not based on production costs of manufacturing DAA-based pills.

Here is an illustration by Dr. Freeman about how the new standard sofosbuvir-based Hepatitis C treatment costs, and what are the actual production costs for making it.
hepatitis c treatment price

From the graph above, it is clear that Hepatitis C treatment pricing has nothing to do with the cost of ingredients. Pharmaceutical companies spend $100 to produce Hepatitis C drugs, and sell it for outstanding $84,000 (US price). This incredible margin indirectly translates to 500,000 death every year.
Paradoxically, the discovery of an effective Hepatitis C cure brought more problems than it solved due to how Big Pharma operates.

There is a way around Big Pharma. One of the main objectives of REDEMPTION-1 clinical trials is to provide a scientific basis for treatment with the generic DAAs. It was designed to prove a patient can be cured using the low-cost generic DAA as effectively as with $84,000 priced branded medicines.

Generic DAA and the legality of obtaining it

Generic DAAs are basically the main therapeutic ingredients that branded Hepatitis C medicines are made of. It is important to understand that DAAs hold all of the therapeutic effect; pharmaceutical companies usually add sugars and other non-therapeutical ingredients to transform DAAs in powder form into a pill; a product most of us are used to.

According to the study, generic DAAs such as sofosbuvir, ledipasvir and daclatasvir are being mass produced for 1% of the current US price of final products. By using these DAAs for treatment, we can forgo 99% of costs connected with Hepatitis C treatment. However, in many cases legality of using the low-cost generic DAA is put under question. These issues are very important when it comes to obtaining low-cost treatment and were addressed at the International Liver Congress 2016 in Barcelona.

Dr. Freeman pointed out that according to the governing laws of Australia, the UK and other countries, an individual patient has the right to import the maximum of 3-months worth of supply of medicines intended exclusively for personal use.

In the pharmaceutical industry, usually the Big Pharma has patents on therapeutic molecules lawfully giving them monopoly power and privileges. The Hepatitis C treatment are no exception; DAAs such as sofosbuvir, ledipasvir and daclatasvir are all protected by patents. 
Nonetheless, World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) provides a basis why importing Hepatitis C medicines such as generic DAAs is legal.
According to Article 60 of the said agreement known as De Minimis Imports, the following is stated:

"Members may exclude from the application of the above provisions small quantities of goods of a non-commercial nature contained in travellers' personal luggage or sent in small consignments."

The quotes article states that the TRIPS laws exclude the import of small quantities of non-commercial goods. A Hepatitis C patient travelling out of China with generic DAA pills in his backpack for personal use is an example of practical application of De Minimis Imports article. This also provides a legal basis for fixhepc.com to provide Hepatitis C patients with access to medications and helps them by discussing the treatment on-line.

REDEMPTION-1 Clinical Trials

In order to start the REDEMPTION-1 clinical trials, two key elements were needed:
  1. Credible generic DAAs as treatment.
  2. Hepatitis C patients as subjects.

Generic DAAs

Generic DAAs were obtained and their quality was evaluated with advanced pharmaceutical techniques such as HPLC, NMR and Mass Spectrometry. To a trained eye, the results obtained (included below) prove that the obtained sofosbuvir DAA has a molecule structure expected from sofosbuvir molecule. This confirms the validity of the generic DAAs used in the REDEMPTION-1 trials.

sofosbuvir nmr
The peaks in the NMR spector above correspond to specific hydrogen (H) atoms within the molecule of sofosbuvir and confirm the structure of the whole molecule. NMR is a standard technique for obtaining the molecule structure of small therapeutic molecules such as DAAs.

Hepatitis C Patients

In order to determine the effectiveness of the obtained generic DAAs, Hepatitis C patients were recruited via http://fixhepc.com/ website. With the help of Dr. Freeman, more than 400 patients were assisted in making a personal importation of the affordable Hepatitis C medications.
redemption trials

As one can clearly see, the patients from all over the world were included in the trials. Each of them were given an assistance in legally importing the verified generic DAA treatment for an affordable price.

Using the gp2u.com.au Telemedicine Platform each patient was assessed in three stages:
  1. Before treatment
  2. During treatment
  3. After treatment (determining the cure rate via sustain virological release (SVR))
This system presented the basis for assessing the safety and efficacy of the generic medication legally imported by Hepatitis C patients.

It is well known that there are 6 genotypes of Hepatitis C virus and each of them is treated in a respective manner with a selection of generic DAA. From the poll of over 400 Hepatitis C patients, Dr. Freeman presented the statistical data about the patients involved in the trials.
hep c basic characteristics of patients in trial
The statistical data above reveals that the average age of Hepatitis C patient in the trials was 54.4 years. About half of the patients were naive - meaning they received no previous Hepatitis C treatment, and about 30% of them have already suffered liver cirrhosis.

The most predominant genotypes in the trials were genotype 1 (63.9%) and genotype 3 (27.5%), and the most predominant manner of treatment was sofosbuvir+ledipasvir (45.8%) and sofosbuvir+daclatasvir (42.6%).

REDEMPTION-1 Trials Results

The objective of the trials was to evaluate the safety and efficacy of generic DAA treatment and compare them with published data from Phase III clinical trials of existing branded Hepatitis C treatments.

The main parameter for measuring the efficacy of Hepatitis C treatment is the decrease in the viral load over time.

In the graph below, we can see the comparison of how quickly does the HCV viral load decrease in patients treated with the generic DAA. Added to the graph are the results of Phase III clinical studies of how quickly did the HCV viral load decreased in patients using branded medicines.

viral response redemption trials vs published data

Reading the graph, it is important to see that when Log Viral Load reaches 1, there is no more HCV virus present (since log(1)=0). The results of REDEMPTION-1 trials clearly indicate that the decrease in viral load in patients treated with generic DAA is as quick, or in some cases even quicker, than in patients treated with branded medications. This confirms the premises that the efficacy of generic DAA treatment is comparable to that of the treatment with branded medications.

Here is a more detailed look of how generic DAA treatment combination sofosbuvir+daclatasvir is fighting off HCV in patients with genotype 1 and genotype 3.
gt1 vs gt3

As we can see, the viral load of genotype 1 patients has decreased to 0 (Log Viral Load = 1) faster. In average, it took about 14 days of treatment for genotype 1 patients to be free of HCV. For genotype 3 patients, the zero viral load was achieved in about 30 days.
In both cases, the sofosbuvir+daclatasvir combo was proven to be very effective in curing Hepatitis C.

What was the cure rate in REDEMPTION-1 Trials?

A parameter that is observed when we want to determine if a patient is cured of Hepatitis C, is the viral load (HCV RNA). If we cannot detect the genetic material RNA of HCV in the performed test (this means that the content of HCV RNA is below the lower limit of quantification (LLOQ)), we count such a patient as cured.

However, some patients who show zero viral load at the end of treatment (EOT), will in some weeks again suffer from Hepatitis C. Some of HCV viruses were not destroyed and evaded detection; without treatment they will multiply and we will again see their presence via measuring the viral load. 

In the graph below, we see the efficacy of treatment at 2 distinctive time points:
  • At the end of treatment (left columns)
  • 4 weeks after the end of treatment (right columns)

hepatitis c end of treatment and svr4
At the end of the treatment, the resulting cure rate for the most prominent treatment regimens was 99.6%. Out of 236 patients treated, only 1 still showed a non-zero viral load at the end of the treatment. The viral load of the rest 235 patients was zero.

4 weeks after treatment, however, some patient experienced the Hepatitis C recurrence. From the data for GT1 above, we can see that the treatment combo sofosbuvir+ledipasvir went from being 99.2% successful to being 93.7%. This means that in 5.5% of patients treated in such a way, Hepatitis C came back.
On the other hand, sofosbuvir+daclatasvir combo was more successful - the cure rate after 4 weeks fell to 97.3% from 100%. Essentially, only 1 patient with GT1 treated in such a manner suffered from Hepatitis C recurrence.

The main result of REDEMPTION-1 Trials - EFFICACY

The REDEMPTION-1 trials main objective is to scientifically prove that the generic DAA medicines patients can purchase for about $1,000 are equally successful in curing Hepatitis C as branded medications for which the US patients have to pay $84,000 or more.

The overall cure rate was observed via parameter SVR12 - sustain virological release measured 12 weeks after the end of treatment. It is a consesus that SVR12 is a true measure of Hepatitis C medication efficacy.

In the graph below are the cure results of branded medications for each genotype.

published svr12

Here are the cure results as obtain with generic DAA treatment in REDEMPTION-1 trials. 

generic daa svr12
By comparing the above graphs, we can see that the cure rates in branded medicines treatment and low-cost generic DAA treatment are very similar.

This is the confirmation of REDEMPTION-1 trials objective.

Accordingly, we see less than 6% difference in cure rates between branded medicines and low-cost generic DAA; what is more, in more cases the treatment with generic DAA has proven to be even more successful than with the branded medications.

The main result of REDEMPTION-1 Trials - SAFETY

Dr. Freeman also addressed safety evaluation of the generic DAA treatment. As you can see from the presentation slide below, the safety profile of patients included in the study was comparable to the findings of Phase III clinical studies for respective branded medications.

hepatitis c safety

Conclusions of REDEMPTION-1 Trials

The successful REDEMPTION-1 trials have proven that the Hepatitis C treatment with the generic DAA is as effective and safe as with branded medications.

In order to summarize the results of the trials, Dr. Freeman pointed out 3 very important things to remember:
  1. Generic cure for Hepatitis C is as effective as branded medications, and it only costs $1,000.
  2. Given $200 costs of production of sofosbuvir+daclatasvir API, the possibility of $200 Hepatitis C cure is now (not in the future)
  3. There are 150 million Hepatitis C patients in the world. Without low-cost affordable treatment the future of majority of Hepatitis C patients looks like this (check the photo below)
hep c future

The successful trial is being praised all over the news. Here are some stories about how the REDEMPTION-1 trials might influence Hepatitis C treatment in the future.
  • http://www.eurekalert.org/pub_releases/2016-04/eaft-lgd040816.php
  • http://ilc-congress.eu/news/
  • http://www.aidsmap.com/page/3050874/
  • http://hepatitiscnewdrugs.blogspot.si/2016/04/generic-direct-acting-antivirals-for.html
  • http://www.medscape.com/viewarticle/862085

 
The International Liver Congress is a 5-day event where scientists and medical experts from all over the globe come up to speed with what is new in the latest liver research. Arguably, it is the biggest event connected with liver diseases in general, and has the biggest impact factor. This year, more than 10,000 scientific and medical experts met at The International Liver Congress 2016 in Barcelona, Spain. The spotlight of the congress was on what new research says about the possibility of treating liver diseases, and the center was taken by Hepatitis C - the ongoing high prices of Hepatitis C treatments were challenged and alternatives presented.

Dr. Freeman of FixhepC Buyers Club gave one of the most convincing presentations by tackling the most important issue in Hepatitis C treatment today - the high prices of branded drugs coming from Gilead Sciences, Abbvie, BMS and MSD. From the data gathered during large-scale clinical trials with DAA treatments, it is evident, as Dr. Freeman himself pointed out, that patients who cannot afford more than $80,000 for branded Hepatitis C drugs can be treated with DAA with equal success rate. The upside of DAA treatment is the low cost - Hepatitis C patients from all over the world can be cured for as little as $1000.

By proving the generic DAA treatments to be as successful as branded treatment, Dr. James Freeman defined a clear role of generic medicines in Hepatitis C treatment area.

Dr. Freeman's Idea

The International Liver Congress was always a very notable event; however, in recent years the interest and people coming to the event started picking up tremendously. Obtaining a new Hepatitis C cure is a part of the reason why; the other part is that by inventing a very successful Hepatitis C cure, this treatment area became very profitable for everybody who is selling branded Hepatitis C treatments. 

One look at the table of the most expensive prescription drugs in the US will tell you why Hepatitis C treatment sell, and they sell for ridiculously high prices.


However, for everybody who can afford Hepatitis C treatments like Sovaldi and Harvoni, there are at least 10 people in the US and around the world who cannot even phantom how to raise $80,000 for the treatment without which they will in all probability die.

Generic Hepatitis C market

The secrets of the success of modern Hepatitis C treatments are the newly found active molecules in branded medicines. These active molecules, which carry all the therapeutic effect, are known as direct-acting antivirals or DAA for short. Because how the Big Pharma works, the DAA such as sofosbuvir, ledipasvir and daclatasvir are readily available in pharmaceutically-based manufacturing companies in India and China. 

Dr. Freeman's idea was simple but has a profound effect: Why not use these low-cost DAA, from which branded Hepatitis C treatments are made off, to treat Hepatitis C?

With the redemption trials, Dr. Freeman went out to establish how well do the DAA cure Hepatitis C in comparison with branded drugs such as Sovaldi and Harvoni. The upside, of course, is a huge reduction in Hepatitis C treatment cost. If the DAA work, a patient with Hepatitis C would no longer be asked to pay more than $80,000 for the treatment; he or she will have an alternative option to be treated with DAA for about $1,000. In such a way, millions of Hepatitis C patients all over the world can get an access to the treatment because of it's financial availability.

DAA Redemption Trials

The purpose of DAA redemption trials was to establish how well do the DAA treat Hepatitis C. We know the cure rate of the majority of branded Hepatitis C treatments is above 90% according to respective Phase III clinical trials done by Gilead Sciences, Abbvie, MSD and BMS.

For the purposes of the trials, the low-cost DAA such as sofosbuvir, ledipasvir, daclatasvir and ribavirin were legally imported and tested with modern analytical techniques such as HPLC, NMR and mass spectrometry. Patients involved in redemption trials came from all over the world - US, UK, Australia, Canada, Europe, SE Asia and Africa.

“Our interim data suggests a potential solution for Hepatitis C patients in areas where treatment access has been restricted as a result of the high prices demanded for branded treatment,” said Dr. James Freeman, the lead author of the study. “At the price level of generic direct-acting antivirals, treating the entire global Hepatitis C epidemic could be financially feasible. Furthermore, if a patient is cured of Hepatitis C, there is evidence for improved survival, and lower risks of liver cancer and liver cirrhosis and cured patients could return to work, delivering further economic benefits to society.”

Trial's results clearly indicate that generic DAA treatment is successful in overall 95% cases in patients with the most common genotype 1. More importantly, this is in line with how well branded medications performed in their respective Phase III clinical trials. This serves as a proof that being treated with banded medication will yield the same results as with generic DAA treatment - however, by choosing the later, you will save $80,000. Not only that, all the patients who cannot afford to fetch up $80,000 will now have an excellent fighting chance by choosing the $1,000 DAA treatment.

Results:
The cure rate for sofosbuvir + ledipasvir (branded medicine: Harvoni) in genotype 1 Hepatitis C patients is 93%.
The cure rate for sofosbuvir + daclatasvir (branded medicine: Sovaldi + Daklinza) in genotype 1 Hepatitis C patients is 97%.

“Across all genotypes, the SVR rate was 94% after treatment with generic DAAs. This indicates that generic DAAs can deliver the same success rates as branded equivalents, but at a price which is 1/100th of the current cost,” explained Dr. James Freeman.

The Implications of Successful DAA Redemption Trials

About 15 years ago, instead of Hepatitis C, we were dealing with high prices and resulting lack of availability for HIV drugs. People were dying not because of the lack of treatment but because the treatment was too expensive for most of them to afford.

Today everybody infected with HIV is treated with very effective and affordable treatment.

If there was one defining moment in history that changed our view of HIV from a deadly disease to an easily-treatable one, it was a 2004 Lancet published study that proved the same for HIV as Dr. Freeman demonstrated for HCV - Generic medications work as effectively as the originator's medication for a fraction of the cost.

Because of the impact factor the International Liver Congress has, we don't need only to hope for Hepatitis C to be as easily treatable as HIV in 15 years - we can count on it. From an average patient to the US Senate, everybody is pushing for lower cost of Hepatitis C drugs; but as of yet the Big Pharma could not be reasoned with.

Thankfully to Dr. Freeman we don't need Big Pharma to lower the costs any more; now we have a definitive proof that the low-cost generic DAA treatment is equally successful as the drugs Big Pharma wants to sell for above $80,000. We can do it for $1,000 and in such a way we can help everybody - not only 6-figure income people in the US, but a farmer in Australia or a sheep herder in Egypt as well.

“There is a clear role for generic treatments such as these for people with Hepatitis C across the world. The implications of increased availability of these drugs could be enormous, presenting more people with the possibility of a ‘cure’ for what is often a debilitating condition,” said Professor Laurent Castera, EASL Secretary General.

We will give you an inside scoop on the details of the study from Dr. Freeman's presentation in our next blog post. If there is one thing to remember from all of this, it is that when Dr. Freeman was done with the presentation a few light bulbs went off above scientific and medical experts heads - the idea that we can cure the whole planet of Hepatitis C, and we can actually afford to pay for it is a reasonable one.

In the video below you can see the highlights from the International Liver Congress 2015. The video for 2016 highlights is currently in production.

https://www.youtube.com/watch?v=btubKE6OZYg


 

One poignant post that says it all...

Thursday, 14 April 2016 18:26 Written by
Thank you all, I wish I could say Harvoni cured me, but it did not. Generic sofosbuvir and ledipasvir from China did. I would still be very sick without it.

Gilead is a hedge fund under the guise of a pharmaceutical company. They want drugs that will treat diseases that are problems in wealthy, industrialized nations. Don't look for them to come up with a cure for malaria, ebola or Zika-there is just not enough money in it for them to be interested.

They will continue to tend the geese that lay the golden eggs until, like Australia, they are forced to "make the deal". Then they will cook and eat them.

In the US, insurers are relaxing restrictions because of legal pressure brought about by patients over denial of treatment. This will force substantial rises in the cost of health insurance for everyone, with Gilead getting the money. Health insurance companies don‘t go broke. They have reserve funds, and when they have to tap into them one year, they raise the premiums the next to cover the shortfall.

Widespread acceptance of affordable generics is the only way Greediad will have its hand forced. Dr. Freeman's EASL presentation on the stellar findings of the REDEMPTION clinical trials tomorrow could be a major first step.

We are in a high stakes poker game here. The insurance companies are the "house”- Gilead, the well-funded, card-counting professional gambler.

We are the chips.

$300 Hepatitis C Cure Could be Available Within 2 Years

Thursday, 14 April 2016 09:12 Written by
14th April 2016 - The world renown International Liver Congress 2016 started yesterday. One of the current highlights is a study by DNDi (Drugs for Neglected Diseases initiative) which introduced a new ravidasvir and sofosbuvir combo for treating Hepatitis C.

According to clinical studies done on 300 patients in Egypt, the new Hepatitis C combo is 100% successful in curing Hepatitis C. What is more, DNDi predicts this medicine will be available in the US, Europe and Japan for - brace yourself - less than $300.

$300 instead of $80,000 for curing Hepatitis C

Hepatitis C was not a big market for pharmaceutical industry prior to 2013. Gilead Sciences, a pharmaceutical giant, launched Sovaldi (400mg sofosbuvir) in December 2013; this is when everything changed. Hepatitis C became one of the most important therapeutic areas for Big Pharma.

Sovaldi was a stellar achievement and raised the cure rate in Hepatitis C patients from 50% to over 90%. But what made the headlines was it's price point - $80,000 for a single treatment. This transformed Hepatitis C treatment area to one of the most lucrative and profitable areas Big Pharma can find themselves in. 

The extreme pricing of Sovaldi led to the extreme pricing of other Hepatitis C medicines which were launched after Sovaldi. Viekira Pak, for example, was launched by AbbVie with a price  $83,320 per treatment. In fact, if you check the most expensive drug on the planet list, you're bound to find all Hepatitis C drugs on it and not one of them has a price tag less than $50,000 per treatment.

This is why DNDi's study is so important. It seems that the drug combo they develop is working even better than what Big Pharma came up with, and they are willing to give it to patients for mere $300. This is more than 99% price reduction in Hepatitis C treatment

DNDi is a non-profit organisation and factors only the manufacturing costs and the costs of running the DNDi into the final cost of medicines. This is how the $300 price tag can be achieved. One has to ask if Gilead has the same costs, why does it charge $94,500 for Harvoni in the US? That means that $300 goes to the manufacturing, and $94,200 is counted as net profit from each and every patient.
dndi
By now pretty much everybody knows the story about how Martin Shkreli lifted the prices of HIV medications from $13.50 to $750 per pill. DNDi is doing just the opposite; they will try to reduce $1,000 per pill standard to $3.50 per pill.

Ravidasvir and Sofosobuvir combo clinical study in Egypt

DNDi teamed up with Egyptian pharmaceutical company Pharco Pharmaceuticals to conduct clinical studies in Egypt. 300 genotype 4 Hepatitis C patients were included in the study, and the cure rate is between 98%-100%. This showed principle investigators that one does not need to use ribavirin in order to successfully cure genotype 4 Hepatitis C. 

DNDi is of an opinion that the new Hepatitis C drugs for $300 will be available in Egypt within 12 months. On the other hand, they are starting to conduct clinical trials in Malaysia and Thailand where patients have different underlying genetic characteristics. Upon successful trials, we are be expected to see Hepatitis C cure for $300 within 18 to 24 months. The drugs will be available in developing countries as well as developed countries. However, bringing such low-priced medicines to markets dominated by pharmaceutical giants such as Gilead Sciences, Abbvie, BMS and MDS might be challenging. 

What are Hepatitis C patients to do?

An average Hepatitis C patient should right now be asking the following question 'Do I buy Harvoni for $94,500 or wait two years and buy this new Hepatitis C combo for $300?'. The difference is ground-breaking. 

Patients are currently paying more than $1,000 per pill of Sovaldi or Harvoni, and they usually need 84 of them. Pharco Pharmaceutical is expected to produce and sell the drugs that have the same or even better effect on Hepatitis C for $3.50 per pill. 

The answer what to do: it depends from patient to patient. The most basic idea is to consult with your doctor about waiting for the new medication. It might suit your wallet, but if your liver deteriorate too much during this period, the size of the wallet won't matter any more. 
By now pretty much everybody knows which common disease will your wallet hate the most: Hepatitis C.

Let us look at a list of the most expensive drugs in the US. There are top 10 on the list; can you guess how many of them are Hepatitis C treatments?

We will explain an extraordinary story why all of these Hepatitis C drugs found their way on the list. In 2011, the highest expected price point for Hepatitis C cure was $36,000. Now patients are paying more than $80,000 for the privilege. What happened?

The real prices of the most expensive drugs in the US.
most expensive drugs in the us
As you can see in this summary by Medscape, 5 out of 10 most expensive drugs in the US are Hepatitis C treatments. Gilead Sciences takes the 1st and the 2nd price with their extremely highly priced sofosbuvir-based treatments Sovaldi and Harvoni. 

How Sovaldi Came to the US Market

Sovaldi and Harvoni are marketed by a pharmaceutical giant Gilead Sciences. They were the ones who got the market authorisation approval by the FDA in December, 2013, and launched Sovaldi - the first all-oral Hepatitis C cure. Without a doubt, the first effective Hepatitis C cure was a game changer. It didn't only change how we perceived Hepatitis C but how we see pharmaceutical industry as a whole. The reason? Just look at the current Sovaldi price point - above $80,000 per a single treatment.

Pharmaceutical companies often try to justify high costs of drugs because of all the research and development that went into finding the innovative new drugs. Admittedly, R&D costs are high and rising, but Gilead Sciences was a bit shy to use R&D costs and innovation as an excuse for the extreme pricing of Sovaldi. Why?

R&D Costs for Sovaldi were very low

The reason is because Gilead Scienced didn't do all the R&D job themselves; they didn't even do the majority of it. The necessary R&D was done by  Pharmasset, a pharmaceutical company that was bought by Gilead because of its wonderful sofosbuvir molecule (Sovaldi consists of 400 mg sofosbuvir pills). Pharmasset has done the majority of work, and in their SEC filing in 2011 they projected that when the sofosbuvir-based drug will be finished and launched, 'a U.S. base rate of $36,000 per course of treatment' will be applicable. So how did we come to $80,000 price tag for Sovaldi?

If there was a single identifiable moment when Hepatitis C patients should scream at the tops of their lungs, it was the 2011 purchase of Pharmasset by one Gilead Science Inc.. Gilead paid $11.2 billion for a company with the ground-breaking Hepatitis C molecule. All they had to do, is just bring the research to conclusion, launch it and Hepatitis C patients would be well off, knowing they have an affordable medicine.

Instead, Gilead Sciences made a giant correction in the price of new Hepatitis C treatment. They raised what was supposed to be $36,000 cure into $80,000 cure. Given that patients don't really have a choice, Gilead put their bets on a sole premise that patients would rather pay $80,000 than die. And it paid off in a big way. 

Gilead Sciences stock after Pharmasset purchase
gilead sciences stock after pharmasset purchase
When Gilead bought Pharmasset, its shares were trading below $20 and the company's market capitalisation was less than $30 billion. Gilead was a small-to-middle-player in the biotech industry.

In two years it took for Gilead to turn sofosbuvir molecule into Sovaldi medication, its shares were trading 300% higher at $80, and had a market capitalisation near $100 billion. Sovaldi has single-handedly made Gilead Sciences into a biotech giant it is today.

What has Gilead actually done? 
Bought another company and harvested the fruits of their labor. It's just like a normal person going to the store, buying a dishwasher and selling the washed dishes for $1,000 a plate. Gilead just brought it home in a big way. 

Lack of Innovation

The key active ingredient that goes into Sovaldi and Harvoni is sofosbuvir; this is why Pharmasset was bought for $11.2 billion. In hindsight, combined Sovaldi and Harvoni sales will probably peak over $20 billion in sales - if Gilead has done something right, it was its purchase of Pharmasset. 

Sofosbuvir enables Hepatitis C treatments to be even more than 95% successful in curing Hepatitis C. However, despite the miracle effect, the molecule is not something all that new. If a medical chemist would compare sofosbuvir with acyclovir, standard antiviral, he would see some difference but practically the same bone structure of the molecule. Sofosbuvir is just a bit tweaked, that's all.

Acyclovir (left) and Sofosbuvir (right) - Molecules are different but the principle of how molecular structure affects Hepatitis C is the same
acyclovirsofosbuvir












In the developed world, this tweaking means innovation. However, India did not find the Gilead's new sofosbuvir molecule all that different from other similar antiviral active ingredients. They stated that Gilead failed to showcase a significant innovation and this is why India did not grant patent rights to Gilead for their Hepatitis C drugs. Gilead had to struck a deal with Indian pharmaceutical companies to generate its Hepatitis C drugs and sell it for about $1,000. One has to ask - if they can sell Sovaldi for $1,000 and still turn a sizable profit, why are they selling Sovaldi for more than $80,000 in the US? How much profit are they making by selling drugs to people who would die without them?
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