In the world of Hepatitis C patients, Twinvir started to pick on mythical proportions. It seldom happens that a generic drug, no matter how successful, becomes so quickly known to the patients who need it. Twinvir pills (sofosbuvir 400 mg / ledipasvir 90 mg) produced by Incepta Pharmaceuticals in currently one of the best-selling generic medications in the world. How did these pills from Bangladesh get so popular and well known?

Twinvir is a generic version of Harvoni - Meet Joe

Let's put ourselves in the shoes of Joe, a Hepatitis C patient, in late 2013. When Joe was diagnosed with genotype 1, he was told that he had Hepatitis C for more than 10 years but now things are starting to go bad for his liver. He needs a cure as soon as possible.

At that time the only cure available was treatment with interferon injections and supplemented by ribavirin pills. If Joe went with this treatment, there were 50% chances he'll get well in half a year. However, there is also 50% of chances that his liver will not respond to treatment.

New sofosbuvir-based treatment

buy twinvir online

Luckily, in December 2013 he got another option for treatment. Gilead Sciences, a pharmaceutical company, had just developed and started to market a Hepatitis C wonder drug called Sovaldi (sofosbuvir 400mg). According to clinical trials, the cure rate is more than 90% in only 12-week treatment. The newly developed Harvoni is even better. With his life in danger, Joe was very happy to see the miracle of modern science and was more than willing to go on treatment. 
However, what Joe did not plan is the price of the treatment. The price tag of Harvoni was $94,5000 per treatment. The meds do save lives but $94,500 is still a very large sum. This is where Twinvir enters the story.

Twinvir in third world countries

The company producing Harvoni, Gilead Sciences, was reaping sales record all over the US and Europe. However, they had major problems with third world countries - not only did they knew barely anybody in lets say India or Egypt will be able to afford the medicine at high prices, India additionally challenged Gilead because of the lack of innovation that went into developing the sofosbuvir molecule (it really does look like other antivirals). Consequently, as a matter of good will, Gilead gave licences to several Indian and other companies, including Incepta Pharmaceuticals, to produce generic Sovaldi and Harvoni. 

Twinvir is thus a miracle drug that was brought to market with quite a miraculous way. Usually, pharmaceutical companies use patents on molecules to keep generics out of the game for 10 years or more. However, Twinvir was being produced, sold and used for treatment only a good year after the first launch of Sovaldi. Produced in Bangladesh, many Hepatitis C patients from the US, Australia and Europe were looking a way to get the necessary medications - but why looking for Twinvir when you have the original version of Harvoni at your local pharmacy?

Twinvir cost - A $1000 price tag

Here the main reason why our patient Joe decided to go to Bangladesh and produce Twinvir - the cost of Twinvir. While Harvoni in the US costs $94,500, exactly the same pills (generic version) costs less than $1,000 in Bangladesh and India. This miraculous drug at low cost is known as Twinvir, and because many patients had a very good incentive to get it, Twinvir's availability and recognition came with it. 

There is a major difference between price of Twinvir and Harvoni but no difference in effectiveness. Generic medications have to be by regulation of equal effectiveness (measured by comparing bioavailability of both Twinvir and Harvoni) than the originals. What is more, in this case Gilead practically have the plans how to create sofosbuvir pills to Incepta as a part of their licencing agreement. 

Hepatitis C tourism to India to get Twinvir and other Hepatitis C drugs

When Gilead representatives were asked how will they fight patients seeking the low-priced Twinvir and other sofosbuvir-based medications from India, Gilead EVP Gregg Alton told the news service: "We aren't surprised; we knew this was going to happen. This is a reality of having these types of programs. As soon as a gray market develops, there isn't much we can do to control it at a pharmacy level."

In short, patients who are going to die without a cure, will rather seek out $1,000 cure than the $94,500. This is not surprising but it may not be 100% legal to do so. Nevertheless, as Gilead has little control over what patients can do, there is another factor to include - a moral factor. It is understood that pharmaceutical companies spend money for drug research, development, marketing and other costs, and still reap the enormous corporate profits. However, from moral standpoint, when lives are at risk, the business model should at least party change. In other words, if you have developed a cure for Hepatitis C, you are at least partially obligated to help Hepatitis C patients. 

What Gilead is actually doing is putting enormous price tags on the developed drugs - which is more considered health profiteering than helping people in need. People seeking Twinvir overseas is a natural response of the population that desperately needs the medicines. If you can get a whole treatment regimen of Twinvir for a single pill of Harvoni, you will be very inclined to buy it. 

In the end, Joe will more than likely decide to buy Twinvir than Harvoni. 

Here you can see a short video about Incepta's Twinvir, a low-cost version of Harvoni.

Twinvir on FixHepC.com forum

We had a lot of talk about Twinvir on our forum at FixHepC.com, and you're welcome to see what opinions patients had shared about Twinvir and ask them anything about the meds. Remember, they are the ones who have first-hand experience with it. You can access our forum here.

As always, there is a very easy and save legitimate way of getting generic Sovaldi or Harvoni. You can contact Dr. James Freeman and us and we'll help you get the medicines you need.


 

Gilead Sciences, a pharmaceutical giant, has launched very effective yet pricey drug for the Hepatitis C patients. The company justifies the $94,500 price of Harvoni and $84,000 for Sovaldi for a 12 week course on the basis of its success rate at curing the disease and preventing future costs of hospitalization, liver cancer and transplants.

Discovery of Sofosbuvir - One of the most effective Hepatitis C treatment molecules

The drug can save the patient from spending a fortune on a new liver if everything else fails. Gilead Sciences put billions of dollars in research and development; the result was the discovery of sofosbuvir - an active drug molecule that treats Hepatitis C. 400 mg of Sofosbuvir is present in Sovaldi costing around $1000 a pill while Harvoni is comprised both of sofosbuvir and ledispasvir. The price of a single Harvoni pill is $1,125.

Gilead gives licences production of Sovaldi and Harvoni in India, driving down the costs

The cost of treating Hepatitis C is very high in the U.S. and the insurers, employers and U.S. Health programs have raised an outcry against the hefty price of Harvoni. However, Gilead Sciences gave license to produce generic versions of Harvoni to several Indian generic pharmaceutical companies. Since majority of Indian population earns much less than the US population, India has been treated as a special case and the Indian government has negotiated a deal with Gilead to produce Sovaldi at $300 per bottle and $900 for 12 weeks course, costing just 1% of what the treatment cost in U.S. In part this happened because India failed to recognize the innovation by Gilead that went into discovering the miracle Hepatitis C treatment.

Here is how much Harvoni costs around the world.

harvoni cost around the world

Buying Harvoni and Sovaldi in India

There are several generic versions of Harvoni available by licensed Indian pharmaceutical companies at reduced prices, which include drugs like MyHep, Ledifos, Hepcinat, Twinvir, Hepcinat LP and Hepcvir. Thus, there has been a rise in Hepatitis C Tourism as more and more patients are flying towards India to get cheaper treatment for their disease. The patients without sufficient insurance to cover the costs of Harvoni are already on the move; there is no Medicaid or state-funded program available for them in the U.S. so they are jetting to India for treatment.

One of the patients landed in Chennai and apart from his $2000 travelling and hotel expense, he paid $1000 for the treatment and saved US$80,000.

Ordering Harvoni Online

However, the patient of Hepatitis C does not necessarily have to travel all the way to India to get the medicines which they can conveniently order online. Although, in most cases, buying medicines online is mostly discouraged, but there are some reputable and credible suppliers such as FixHepC.com that deliver life-saving Hepatitis C treatment worldwide in just 1-3 weeks.

If you go on your own, this is what you need to do: you need to contact credible pharmaceutical companies in India that have been given the license to produce generic Harvoni and talk to them about your condition. You need to send a doctor’s prescription and identity proof and an invoice will be sent by their side. You will be required to give your address and chose the payment mode to place the order. Once the payment has been made, the drug will be shipped to your home. Although, travelling to India for the treatment of Hepatitis C is a common sight and companies are even setting up medical related trips for their employees, but it is more a feasible option to order the drug online from licensed companies and save the travelling expense. In the end, the main purpose of the Hepatitis C patients is to get the drug which does not necessarily means to travel abroad.

If you let FixHepC.com help you, we will arrange everything for you and secure shipment of active molecules such as sofosbuvir and ledipasvir on your behalf. Contact us with your needs and we will work together to get you the Hepatitis C medications you're in need of.
Saturday, 13 February 2016 09:14

How Does Hepatitis C effect the body - Effects of Hep C

Written by
hepatitis c trasmissionHepatitis C is an infection that leads to the inflammation of the liver. Hepatitis C can be transmitted from person to person in various ways; the most predominant via the use of drug injections (60%) as you can see on the pie chart on the right.

What does the liver do?

The liver is responsible for so many essential tasks in the body; it processes blood and filters toxins and ensures no harm will come to your body via their action. The liver is also tasked with producing bile which helps in food digestion, and stores glucose and vitamins. 

Liver inflammation

When the liver undergoes inflammation, it gets extremely difficult for it to carry out all its important tasks. Hepatitis C infection has an effect on the entire body when left untreated for a long time. Hepatitis C has some very subtle symptoms that can be looked out for - its early symptoms include fatigue and yellowing of the skin. These are mild and are unfortunately easily dismissed. As the infection is left free to grow, other serious symptoms such as fever, skin problems and blood disorder may appear.

Liver cirrhosis and the importance of Hep C treatment

Chronic liver infection leads to liver cirrhosis - the scarring of the liver. Treating Hepatitis C early helps prevent serious damage. On the other hand, leaving it untreated for years on end can lead to severe damage of the liver itself, liver cancer and consequently reduction in liver function.

Here is a short intro about liver anatomy and function.

Hepatitis C and Digestive System

The liver performs many functions that are crucial to the wellbeing of the body. One of the most important of which is the production of the substance that is needed to break down fat - bile. The bile is stored in the gallbladder and sent to the beginning section of the small intestine (duodenum). The bile is then combined with stomach acids and digestive fluids from the pancreas; this helps the intestines in absorbing nutrients into the bloodstream. Hepatitis C severely hinders the bile production ability of the liver.

Inflammation also makes digesting food, especially food rich in fat very painful, This causes pain in the upper right portion of the abdomen in infected persons. This is due to a build-up of fluid in the stomach (ascites). A healthy liver produces just the right amount of albumin; this is a protein that helps regulate the amount of fluid in cells; however, a damaged liver does not produce enough albumin and this leads to fluid build-up in the stomach causing pain.

There are some other digestive symptoms to look out for; including vomiting, loss of appetite and nausea. Additionally, stool may become clay-colored or pale, and urine may darken.

Hepatitis C and Central Nervous System

Toxins cause damage to the central nervous system; however, a healthy liver filters these toxins and ensures your body is free of them. When the liver is damaged, it ability to filter these toxins is greatly hampered and the toxins can damage the central nervous system (hepatic encephalopathy). This leads to a variety of symptoms which include weakening of motor skills, sleep disturbances, and sweet or musty breath.

When these symptoms are ignored and the toxins are left to build up, they damage the brain causing confusion, inability to concentrate, forgetfulness and personality changes. If still left untreated, advanced symptoms that may come up include disorientation, agitation, abnormal shaking and slurred speech. In severe cases, a coma might occur.

Hepatitis C and Circulatory System

Apart from the cleansing of toxins from the bloodstream, the liver does the vital function of producing proteins that are needed for a healthy blood and to regulate blood clotting (liver synthesis of coagulation factors). A liver that is not functioning properly creates blood flow problems and increases pressure in the portal vein (the vein that leads to the liver). This causes portal hypertension. Blood is then forced to find an alternate vein to flow through; if a smaller vein is unfortunately chosen, the vein would burst and lead to variceal bleeding (serious internal bleeding).

The liver also extracts iron from the blood and stores it for later use; however, a poorly functioning liver is unable to do that which can result in anemia. Additionally, the liver converts sugars into glucose and then stores it for energy in the form of glycogen. Having too much sugar in the bloodstream leads to insulin resistance and causes type 2 diabetes.

Hepatitis C antibodies in the bloodstream can be detected by carrying out a simple blood test. If antibodies are discovered, it means you have been exposed to the virus. In most cases, a second blood test is needed to confirm a hepatitis C diagnosis.

Hepatitis C and Skin, Hair, and Nails (Integumentary System)

The red blood cells contain a protein molecule called hemoglobin; it helps transports oxygen to cells throughout the body. To obtain and sustain healthy skin, nails and hair, iron is crucial.

Another important substance in hemoglobin is bilirubin. When the liver is incapable of doing its job, bilirubin builds up, causing jaundice (a condition where the skin and the white of the eyes turns yellow).

Hepatitis C and Endocrine and Immune System 

Hormones are regulated by the endocrine system. The thyroid gland which is part of the endocrine system, delivers hormones into the bloodstream. Hepatitis C sometimes causes the immune system to attack and damage thyroid tissues. This can lead to hyperthyroidism (an overactive thyroid); this in turn causes weight loss and sleep disorders.

It can also cause hypothyroidism (an underactive thyroid) which makes you feel and act sluggishly. Research carried out by the Hepatitis Trust has shown that this condition is more prevalent in women than in men.

Today I have some good news for Hepatitis C patients with genotype 1 or genotype 4. In the beginning of February 2016, pharmaceutical giant Merck has entered Hepatitis C treatment market by introducing a completely new drug. Under its trademark, it is known as Zepatier.
zepatier elbasvir and grazoprevir

What is more, Zepatier consists of a completely new set of drug molecules - elbasvir and grazoprevir - and is thus different in the mechanism of action from sofosbuvir-based as drugs by Gilead Sciences, Sovaldi and Harvoni. The major difference between this treatment and all the other Hepatitis C treatment that were recently approved by the FDA is the price of Zepatier. Zepatier costs only $54,600 per treatment in the US which compared with Harvoni's price tag of $94,500 is quite a reduction. However, albeit Zepatier is cheaper and will add competition that will hopefully drive down the prices, the costs of being treated for Hepatitis C are and will in the near future remain enormous. This is exactly why we at FixHepC.com are bypassing the system established and paid for by pharmaceutical industry to provide you with affordable Hepatitis C treatments and make it available for everybody in need of them.

Who is Zepatier for - Genotype 1 and 4

Pretty much anybody having Hepatitis C is aware that there are 6 genotypes of Hepatitis C. If you are wondering what sofosbuvir-based treatment is best for you, you can read about genotype specific treatments here. Not all medications treat all genotypes - for example Harvoni, being arguably one of the best medicines out there, is not used (it is not even registered) to treat Hepatitis C genotype 2.

Zepatier has a more narrow therapeutic potential. It can only be used to treat Hepatitis C patients with genotype 1 or 4. Majority of Hepatitis C patients (54%) are suffering from genotype 1 while only 1% of all patients has genotype 4. This means, roughly speaking, that the new Zepatier drug launched by Merck and approved by FDA is intended to be used in about 55% of all Hepatitis C patients.

Elbasvir and Grazoprevir - Zepatier active substances (APIs)

Before we go into details about Zepatier cure rate (which is comparable with other existing Hepatitis C treatments), let us have a look under the hood of this Merck medicine. APIs or Active Pharmaceutical Ingredients are the ones that make any drug achieve its therapeutic effect. In the case of Harvoni, for example, we have sofosbuvir and ledipasvir as active ingredients, and we already know that for modern Hepatitis C treatment we always use two or more active substances in order to be sure HPV was completely eliminated. 

Elbasvir and grazoprevir are active substances that make Zepatier work. Both of them were originally developed by Merck and designed specifically to treat Hepatitis C. These two molecules represent years of work that Merck's drug discovery department has put in to launch Zepatier. Let us look at elbasvir and grazoprevir more closely. 

Elbasvir Mechanism of Action

The first molecule, elbasvir, has been found to inhibit Hepatitis C virus replication by blocking one of the vital proteins (NS5a) that is essential to the replication process. Elbasvir mechanism of action renders NS5a inactive and thus prevents HPV from making more and more viruses. When the replication is stopped, human immune system does the heavy work by targeting and eliminating the remaining virus.

A great thing about elbasvir is that is is very potent and very selective. Potency means that it inhibits NS5a very effectively even at smaller dosages. This is why Zepatier contains only 50 mg of elbasvir. Selectivity is also crucial - elbasvir inhibits NS5a and only NS5a - this means that it does not alter other important processes. Both of these qualities are very important when it comes to Zepatier side effects. Namely, Zepatier side effects are mild because the high cure rate can be achieved with small dosages of a very selective elbasvir molecule.

Grazoprevir Mechanism of Action

Grazoprevir is a second active substance in Zepatier. Instead of targeting NS5a like elbasvir, grazoprevir mechanism of action is directed at inhibiting Hepatitis C virus proteases. With the function that these proteases perform, the HCV is unable to replicate further and is eliminated over the period of several months by body's immune system.

Grazoprevir mode of action is always used as kind of a side-kick of the primary active substance (elbasvir in the case of Zepatier). A good property of grazoprevir is that is useful as a treatment for more resistant HCV genotypes. 

Zepatier Cure Rate and Side Effects

According to clinical studies done by Merck, Zepatier cure rate is very high. For patients with Hepatitis C genotype 1, it was found that Zepatier cures 94-97% of patients. On the other hand, for genotype 4, the numbers are even higher - 97-100% cure rate. You can read everything about how the studies were set up at Merck' Zepatier press release. Some patients are advised to use ribavirin together with Zepatier in order to achieve the best treatment results.

Side effects are mild for a life-saving treatment. These include side effects that are mostly common with other Hepatitis C drugs such as Harvoni and Sovaldi.
zepatier side effects

Here is a list of Zepatier side effects:
  • Nausea
  • Tiredness
  • Headaches
  • Anemia (decrease in number of red blood cells)
  • Stomach pain
  • Allergic reactions (rashes, irritation)
The Zepatier treatment last for 12 or 16 weeks, depending on the genotype and patient's state, and despite the side effects being mild, they can be very bothersome. Having a feeling of nausea for 3 months is not something that one can tolerate with ease.

Zepatier Cost - $54,600 per treatment

The cost of Zepatier is a major think that distinguishes it from other Hepatitis C drugs. Because Merck prices Zepatier at $54,600 per treatment, the drug has already been called a game changer in Hepatitis C treatment. Harvoni, for example, another Hepatitis C treatment, costs $94,500 per treatment in the US.

The much needed competition is here. Zepatier cost might force other big players such as Gilead Sciences and Abbvie to lower the prices of their Hepatitis C medications. However, if you are in need of Hepatitis C drugs, we at FixHepC.com can provide them for less than $2,000. Contact us with your problems and wishes and we will try our best to help every Hepatitis C patient in need.






 

Thursday, 04 February 2016 12:50

Here is why the VA (US Government) owns sofosbuvir

Written by
In the beginning God created heaven and earth. Dr Schinazi created PSI-6130

PSI-6130 www.ncbi.nlm.nih.gov/pmc/articles/PMC1932527/ 

ACKNOWLEDGMENTS

This work was supported in part by NIH grants 5R37-AI-041980, 4R37-AI-025899, 5P30-AI-50409 (CFAR), and RR000165 (to Harold M. McClure) and the Department of Veterans Affairs.

R. F. Schinazi is the principal founder and a former director of Pharmasset, Inc. He is also a major shareholder of Pharmasset, Inc., and Idenix Pharmaceuticals
.

Now PSI-7851 comes directly from the development of PSI-6130

www.wikinvest.com/stock/Pharmasset_(VRUS)/Psi-7851

PSI-7977 (aka Sofosbuvir) is the active metabolite of PSI-7851 so is also directly related to PSI-6130...

files.shareholder.com/downloads/VRUS/0x0...4533817aa73/PSI-7977

So the baby (invention) was born from NIH and VA grant money and was created by someone who was 7/8 time employed by the US Government.

So what you say?

Executive Order 10096, issued by President Harry S. Truman in 1950, I say.

www.tms.org/pubs/journals/JOM/matters/matters-9004.html

The main section of the executive order provides that the government shall obtain all rights to any invention made by an employee if any one of the following conditions applies: the invention is made during working hours; the invention is made using either government facilities, equipment, etc., or is made with the help of another government employee who is on official duty; or the invention relates to the official duties of the inventor.

So what did Dr Schinazi do in 2007-2010 and what were his "official duties"?

This document indicates he was employed by the VA as a research chemist and did indeed make the invention in relation to "the official duties of the inventor" as in on government time, in a government lab.....

tel.archives-ouvertes.fr/pastel-00605911/document

The research presented in this dissertation was performed in the Laboratory of Biochemical Pharmacology (LOBP) at the Veterans Affairs Medical Center/Emory University. LOBP is a drug discovery and preclinical drug development laboratory directed by Dr. Raymond F. Schinazi.

Developed in the 1/8 non government time. This is fantasy, fiction, and BS.

Developed on the government ticket. Owned by the US government.

Brilliant, breakthrough and stellar but not done independently.

And it is all documented.
In a surprising and warm-hearted gesture, the Australian government announced in December 2015 that they will pay for all Hepatitis C medications Australians need. They pledged a whole of $1 billion to the cause.

The announcement came from  Health Minister Sussan Ley, representing Turnbull's government.
Health Minister Sussan Ley hepatitis c

Hepatitis C in Australia by numbers

According to Australian Hepatitis C article, 1 out of 100 people in Australia is suffering from Hepatitis C. With 230,000 Hepatitis C patients, trying to tackle the disease with the new sofosbuvir-based regimen might prove difficult, and it will definitely prove very expensive. 

An additional 10,000 patients per year are being reported. The government went above and beyond claiming they don't only want to try to stop the spread of the disease but wipe it out completely. This is now possible thanks to the newly discovered treatment molecules such as sofosbuvir, daclatasvir and ledipasvir. The older ribavirin molecule is included in the treatment of certain genotypes.

The statement is clear

The government wants to wipe out Hepatitis C within a generation. The treatment will be available to every Australian, even those living abroad, and highlights one of the most daring decisions of Australian government as far as healthcare is concerned. 

How does an average Australian get their hands of subsidized Hepatitis C treatment?

Hepatitis C treatment which normally costs most than $80,000 will now be sold in pharmacies all over Australia for as little as  $37.70 for general patients and $6.10 for concessional patients. The rest of the bill will be paid by the government, according to Minister Sussan Ley. This sounds like a very sweet deal for every Hepatitis C patient and the government is enjoying approval for the help but how likely will the pledged $1 billion help all the patients?

One has to be aware that the price of Harvoni (ledipasvir 90 mg/sofosbuvir 400 mg) for Hepatitis C treatment in Australia is still $80,000. Governments can negotiate these prices but as we've seen in France, UK and Germany, the price was be reduced but not significantly. 

Here is a detailed Hepatitis C factsheet for Australian patients

$1 billion is enough only for 5% of all Hepatitis C patients

Here is the thing. $1 billion is not nearly enough for everybody to get treated. If you do the math, you will realize that at $80,000 per treatment, $1 billion will be used to treat only 12,500 patients. Out of 230,000 registered Hepatitis C patients in Australia, this is still only 5%. 

Annually around 700 patients die because of Hepatitis C or Hepatitis C related illnesses. With the government donation and healing the total of 5% of patients, the number of deaths would theoretically be reduced to 665 people. Which is still a lot.

What can Hepatitis C patients do to get the medicines?

My advice would be to run directly to your doctor and make use of the subsidized medicines - because with such a demand, the funds will soon run out, and 95% of patients will again be struggling to get the medicines.

This is where FixHepC Buyers Club can help you out. We provide you with tested Hepatitis C drugs such as sofosbuvir, daclatasvir and ledipasvir for around $2,000 per treatment (depending on the genotype and treatment). This is quite a reduction in price compared to $80,000 that would need to be paid for the original Harvoni (ledipasvir/sofosbuvir). You can contact us with your inquiries and we will to best of our ability help you.

Hypothetical scenario - What is everybody gets treated by FixHepC provided medications?

Australian government is willing to help eradicate Hepatitis C in Australia with $1 billion. Using the original medicine, this will heal about 12,500 while keeping in mind that every year there are 10,000 new patients. This maths proves this approach being quite ineffective.

On the other hand, FixHepC can offer Hepatitis C treatment for as little as $2,000. With these prices, $1 billion would really go a long way in making Hepatitis C medicines accessible to everyone in need of them. Hypothetically, FixHepC could make a good use of this funds and provide Hepatitis C drugs to 500,000 patients.

This means that all 230,000 Australian patients could be treated and with a 95% success rate of treatment, a great majority of them would be cured. This is a way how Australia could wipe out Hepatitis C in less than a year. What is more, the remaining 270,000 treatments could be used to heal patients in other countries such as New Zealand and Indonesia as well. 

That would be a very important statement in the world. Australia would be looked upon as a country that sees beyond its borders and recognized the need for safe medication of all patients, not just the ones with Australian passports. But in the end, this is more or less just a wishful thinking. 

Step into contact with us and we will help you with Hepatitis C needs. 
Hepatitis C has long been a formidable disease with a high death toll and inadequate treatment. However, in the recent years we have seen much more successful treatment options on a backbone of a newly discovered therapeutic molecule called sofosbuvir

Sofosbuvir is an antiviral molecule, structurally similar to existing antivirals, but it has proven to be of great benefit to Hepatitis C patients - it almost single-handedly skyrocketed the cure rate from 50% to 95% overnight. This has brought the company which brought it to market under the tradename Sovaldi, and later Harvoni, a tremendous success. This molecule is currently the best-selling pharmaceutical ingredient in the world because it plays an essential role in modern Hepatitis C treatment regimen. Today we will have a look at sofosbuvir mechanism of action.

How Sofosbuvir Works

Essentially, sofosbuvir molecule works by preventing Hepatitis C virus (HCV) to replicate itself. One of the necessary components for replication is the RNA molecule of the virus. In order to make a copy of RNA for the new virus to form, a virus uses an enzyme called RNA polymerase to replicate RNA. Basically, out of 1 existing RNA molecules, and additional RNA is formed in order to be used to construct a new virus and facilitate the propagation of Hepatitis C virus - which for a patient means Hepatitis C will manifest more and more in his or her liver.

Sofosbuvir works by inhibiting enzyme RNA polymerase - the cellular worker that performs the replication process. Being unable to make new viruses due to sofosbuvir mechanism of action, the existing Hepatitis C viruses are at the mercy of patient's immune system which is readily eliminating the virus. Without sofosbuvir, Hepatitis C virus has an ability to rebuilt the lost viruses and build up in the liver. When sofosbuvir, however, is allied with patient's own immune system, there is only a 5% probability that the virus will survive (with appropriate treatment regimen). This is why sofosbuvir has a 95% success rate. 

Sofosbuvir Mechanism of Action

Sofosbuvir molecule for mechanism of action
Here is how sofosbuvir molecule looks like in chemical terms. We are about to explain in detail how sofosbuvir works or, in other words, what is sofosbuvir mechanism of action (sofosbuvir MOA).

Sofosbuvir as prodrug

Sofosbuvir is a prodrug - this means that the molecule is chemically changed to a therapeutically useful molecule in a human body. If you look on the structure (on the right); the left part of the molecule remains unchanged while the right part surrounded around P (phosporous atom) will readily change into a therapeutic form with the help of enzymes in the body. In essence, nucleotidyl and nucleoside diphospate kinases are two human enzymes which add phospatic groups to the molecule once the existing groups on P have been cleaved. 

Only when this process and transition from sofosbuvir as prodrug to sofosbuvir as drug is done within the body, the molecule becomes a very effective Hepatitis C treatment.

How does Sofosbuvir enter Hepatitis C virus

The created sofosbuvir drug in the body has to enter Hepatitis C virus in order to be effective in disrupting HCV replication. This is the process that makes sofosbuvir stand out as an effective Hepatitis C therapeutical substance.

It needs to be mentioned that sofosbuvir is not out-of-the-box thinking molecule. Actually, it is very similar to existing antiviral molecules such as acyclovir for example, but one small but very important difference. Every antiviral in this group of therapeutics has to have 3 phosphate groups (Ps in the molecule) to be effective.  Usually, the addition of the first PO 4 -3  phosphate group is the hardest and thus slowest, the other two phosphate groups are then readily added. 
acyclovir mechanism of action
Sofosbuvir was designed to marvelously solve this problem by having the first phosphate group already attached to its structure. Thus there is no need for a lengthy and hard process of adding the group. The other two phosphate groups are quickly added to sofosbuvir and the so-called prodrug is now an active drug.  Of additional benefit are also the groups that are bound to the phosphate group of the molecule - these work by masking the negative (-) electric charge of a phosphate group and by that facilitate the entrance of sofosbuvir into the Hepatitis C virus. 

The results of adding a phosphate group to the original drug is exception. While majority of antiviral molecules were tested to see how effective are they to prevent HCV from either replicating or plain out killing them off, the potency of great majority of them was very low. The added phosphate group separated the mode of action of sofosbuvir from other molecules to such an extent that we don't only see sofosbuvir as very potent; but its ability to suppress HCV spread is so tremendous that the disease as a whole started to be perceived as easily treatable - sofosbuvir had done something no other known molecule was capable of doing - heal 95% of Hepatitis C patients. 

Here is a short video about how Hepatitis C drugs work.
 

Sofosbuvir mode of action

When inside a Hepatitis C virus, sofosbuvir seeks out and selectively attaches to the NS5B polymerase viral protein which is a vital component virus replication. Sofosbuvir mode of action is to disguise itself as a structural part of NS5B. This sofosbuvir mechanism of action is known as a defective substrate. When sofosbuvir binds to the viral protein, it inhibits its further construction. Thus the protein construction is stopped and the protein cannot complete its normal function of replicating the virus. In such a way, the number of Hepatitis C viruses is stagnating and immune system comes in to kill them off one at a time. Without the ability to recover from the heavy losses against the immune system, HCV virus is doomed to be eliminated, which heals the patient of Hepatitis C (viral load goes to zero). 

This is a regular mechanism of action of all nucleotide-like antivirals. For Hepatitis C treatment, other drug molecules are used in Hepatitis C treatment together with sofosbuvir. Mechanism of action of ledipasvir, daclatasvir and ribavirin are not altogether different from sofosbuvir mechanism of action. A natural question is why do Hepatitis C patient have to take two or more drug molecules for treatment if sofosbuvir is already such an exceptionally potent drug with an advanced mechanism of action against Hepatitis C virus?

Why is Hepatitis C always treated with at least two drug molecules?

Sofosbuvir is an extremely effective molecule working against Hepatitis C virus. In fact, sofosbuvir mechanism of action enables it to eliminate more than 99.99% of the virus in a great majority of cases. However, that 0.01% of the virus left could still prove problematic.

This is why a second antiviral molecule is used to eliminate any virus that might have survived. Modern Hepatitis C treatment regimen consist of combination of primarily sofosbuvir, and secondarily ledipasvir, daclatasvir or ribavirin. This is how we can ensure that the treatment is optimal and minimize the risk of HPV developing sofosbuvir drug resistance. 

Experience with viral disease has taught us that virus, which is being endangered with therapeutic drugs, readily mutates and becomes drug-resistant. No drug mechanism of action is capable of completely eliminating the possibility of drug-resistance arising. Especially problematic for the development of drug resistance are viruses that have been treated with a certain drug like sofosbuvir but were not all eliminated. Namely, the remaining ones developed their own mechanism of how to best survive against the drug, rendering them resistant. This is why it is utterly necessary to eliminate all the virus that has come into contact with sofosbuvir or any other therapeutic molecule.

Ledipasvir and Daclatasvir Mechanism of Action

Ledipasvir has the same aim as sofosbuvir - to prevent HCV from replicating; however, the approach it takes is different. Ledipasvir mode of action is to inhibit protein  viral phosphoprotein, NS5A, which is involved in viral replication, assembly, and secretion. The same protein is also targeted by daclatasvir.
 
Hepatitis C has long been a formidable disease with a high death toll and inadequate treatment. However, in the recent years we have seen much more successful treatment options on a backbone of a newly discovered therapeutic molecule called sofosbuvir

Sofosbuvir is an antiviral molecule, structurally similar to existing antivirals, but it has proven to be of great benefit to Hepatitis C patients - it almost single-handedly skyrocketed the cure rate from 50% to 95% overnight. This has brought the company who invented brought it to market under the tradename Sovaldi, and later Harvoni, tremendous success. This molecule is currently the best-selling pharmaceutical ingredient in the world, because it plays an essential role in modern Hepatitis C treatment regimen.

How Sofosbuvir Works

Essentially, sofosbuvir molecule works by preventing Hepatitis C virus (HCV) to replicate itself. One of the necessary components for replication is the RNA molecule of the virus. In order to make a copy of RNA for the new virus to form, virus uses an enzyme called RNA polymerase to replicate RNA. Basically, out of 1 existing RNA molecules, and additional RNA is formed in order to be used to construct a new virus and facilitate the propagation of Hepatitis C virus - which for a patient means Hepatitis C will manifest more and more in his or her liver.

Sofosbuvir works by inhibiting enzyme RNA polymerase - the cellular worker that performs the replication process. Being unable to make new viruses due to sofosbuvir mechanism of action, the existing Hepatitis C viruses are at the mercy of patient's immune system which is readily eliminating the virus. Without sofosbuvir, Hepatitis C virus has an ability to rebuilt the lost viruses and build up in the liver. When sofosbuvir, however, is allied with patient's own immune system, there is only a 5% probability that the virus will survive (with appropriate treatment regimen). This is why sofosbuvir has a 95% success rate. 

Sofosbuvir Mechanism of Action

Sofosbuvir molecule for mechanism of action
Here is how sofosbuvir molecule looks like in chemical terms. We are about to explain in detail how sofosbuvir works or, in other words, what is sofosbuvir mechanism of action (sofosbuvir MOA).

Sofosbuvir as prodrug

Sofosbuvir is a prodrug - this means that the molecule is chemically changed to a therapeutically useful molecule in a human body. If you look on the structure (on the right); the left part of the molecule remains unchanged while the right part surrounded around P (phosporous atom) will readily change into a therapeutic form with the help of enzymes in the body. In essence, nucleotidyl and nucleoside diphospate kinases are two human enzymes which add phospatic groups to the molecule once the existing groups on P have been cleaved. 

Only when this process and transition from sofosbuvir as prodrug to sofosbuvir as drug is done within the body, the molecule becomes a very effective Hepatitis C treatment.

How does Sofosbuvir enter Hepatitis C virus

The created sofosbuvir drug in the body has to enter Hepatitis C virus in order to be effective in disrupting HCV replication. This is the process that makes sofosbuvir stand out as an effective Hepatitis C therapeutical substance.

It needs to be mentioned that sofosbuvir is not out-of-the-box thinking molecule. Actually, it is very similar to existing antiviral molecules such as acyclovir for example, but one small but very important difference. Every antiviral in this group of therapeutics has to have 3 phosphate groups (Ps in the molecule) to be effective.  Usually, the addition of the first PO 4 -3  phosphate group is the hardest and thus slowest, the other two phosphate groups are then readily added. 
acyclovir mechanism of action

Sofosbuvir was designed to marvelously solve this problem by having the first phosphate group already attached to its structure. Thus there is no need for a lengthy and hard process of adding the group. The other two phosphate groups are quickly added to sofosbuvir and the so-called prodrug is now an active drug.  Of additional benefit are also the groups that are bound to the phosphate group of the molecule - these work by masking the negative (-) electric charge of a phosphate group and by that facilitate the entrance of sofosbuvir into the virus. 


 Prior to the discovery of sofosbuvir, a variety of nucleoside analogs had been examined as antihepatitis C treatments, but these exhibited relatively low potency. This low potency arises in part because the enzymatic addition of the first of the three phosphate groups of the triphosphate is slow. The design of sofosbuvir, based on the protide approach, avoids this slow step by building the first phosphate group into the structure of the drug during synthesis. Additional groups are attached to the phosphorus to temporarily mask the two negative charges of the phosphate group, thereby facilitating entry of the drug into the infected cell.[30][31] The NS5B protein is a RNA-dependent RNA polymerase critical for the viral reproduction cycle.
Monday, 01 February 2016 04:00

ASHM Gearing Up For PBS Listing

Written by
Dear Colleague,
 
ASHM is running the Treatment of hepatitis C with Direct Acting Antivirals course at the Rydges Melbourne, Victoria on Saturday, 20 February 2016. This course is being delivered as part of the Control and Elimination within AuStralia of HEpatitis C from people living with HIV (CEASE) project in partnership with the Kirby Institute.
 
This full day, face-to-face course is designed to up-skill the primary care-based workforce in the current assessment and treatment of HCV infection, to enable rapid scale-up of interferon-free therapy with direct acting antivirals (DAA) for HCV. The course is designed for HIV prescribers, but may also appeal to General Practitioners, Sexual Health Physicians, OST prescribers, clinicians working in AOD settings, custodial settings and Aboriginal Medical Services.
 
This is a FREE course, which has been approved for 40 Category 1 RACGP points. A small number of travel scholarships for rural and regional medical practitioners to attend may be available upon request.
 
I have attached a flyer with further details – Feel free to forward to your colleagues and extended networks. To register for this course please go to the courses page on the ASHM website http://www.ashm.org.au/courses.
 
Please do not hesitate to contact me via return e-mail if you have any queries.
 
Kind regards,

Annabelle Kennett
Project Officer
National Policy and Education
ashm | Supporting the HIV, Viral Hepatitis and Sexual Health Workforce
Tel: +61 2 8204 0742 | Fax: +61 2 8204 0782 | E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
LMB 5057 DARLINGHURST NSW 1300 | www.ashm.org.au -

CDC Hepatitis C Infographic

New age Hepatitis C medicines are more than just a medical wonder. They gave humanity an ability to save lives. 

How good are we at saving those lives?

More people die of Hepatitis C than HIV/AIDS

Hepatitis C is a serious disease that ultimately results in death of patients. Approximately 500,000 people die from Hepatitis C and related illnesses in 2013 alone, more than 20,000 of them were US citizens. To put it in perspective: HIV/AIDS has longed been talked about as a very serious disease with a disastrous death toll. However, according to Dr. Laura J. Martin of WebMD nowadays more people die from Hepatitis C than from HIV/AIDS.

Today, there are more than 3.2 million of Hepatitis C patients in the US alone. 

In late 2013, however, humanity had a break-through that should by all accounts drastically change lives of people living with Hepatitis C. A new drug, Sovaldi (400mg sofosobuvir), was approved in December 2013 on the US market.

With it, more than 90% of people with Hepatitis C can be cured. But are they really being cured?

Standard Interferon-based treatment

For any disease to be deemed a very problematic one, there are two conditions:

  1. Disease is serious (causes severe injuries or death)
  2. There is a lack of efficient cure

Polio, for example, was a very serious disease with a disastrous outcome. However, after discovering an efficient polio vaccine, the number of patient and number of death relating to polio was reduced dramatically. 

Hepatitis C prior to 2013 was a very problematic disease because it caused death via liver cirrhosis and liver cancer, and the only treatment we had was 50% efficient. 

Hepatitis C patients were put on 6-months long interferon-based treatment which consisted of injecting oneself with interferon and taking additional oral medicines such as ribavirin (antiviral molecule). Nonetheless, for 1 out of every 2 patients treated the treatment has been proven to be unsuccessful. 

There was a need for an efficient cure. Newly-discovered sofosbuvir molecule was the answer.

New age Hepatitis C treatment - Sofosbuvir-based medications

With the launch of Sovaldi and Harvoni medicines by a company Gilead Sciences, humanity finally attained a very effective cure for Hepatitis C. Being an all-oral regimen, sofosbuvir pills are taken on a daily basis for 12-weeks (standard treatment), have mild side effects and, above all, more than 95% cure rate. This is what in pharmaceutical industry refer to as a game-changer. Now almost everyone can be cured and Hepatitis C suddenly became an easily curable disease. 

Does anybody die of Hepatitis C now?

Simple answer is 'YES'. While the number of deaths has decreased from 500,000 per year, there are still hundreds of thousands of people dying every year. The reason: Hepatitis C.

hepatitis c death statistics

But if we know Hepatitis C is so easily treatable nowadays, why are people still dying?

Pharmaceutical industry is a profitable business (Money>Patients)

When we spoke about Harvoni and Sovaldi being a game-changer in industrial industry, it was meant more in profits than in saving lives. Here are two simple reasons why people even in the developed world are still dying of Hepatitis C.

  1. Original Sovaldi (400mg sofosbuvir) costs $80,000 per treatment (US prices)
  2. Original Harvoni (90mg ledipasvir/400mg sofosbuvir) costs $94,500 per treatment (US prices)

With this in mind, let us calculate the US Hepatitis C market. If we know there are 3,2 million Hepatitis C patients, each in need of an $80,000 cure, the total comes to staggering number: Gilead Sciences is looking to sell more than $250 billion worth of Hepatitis C medicine to patients who can die without it.

Here is a horrifying realization. We have people who will die without the cure. We have the cure. But people who are dying cannot afford the cure because it is priced extremely high. 'What have we come to as a society?' is the right question here.

Way to get Hepatitis C medicines without having to pay massive sums of money

Gilead Sciences, company that markets Sovaldi and Harvoni, offered licences to Indian manufacturers to produce generic version of sofosbuvir-based medicines. In short, India refused to recognise a level of innovation for sofosbuvir molecule that would grant Gilead Sciences a patent and monopoly over Hepatitis C market in India. 

This created a loophole. This loophole is now saving lives. 

FixHepC Buyers Club to the rescue

All around the world there are Hepatitis C patients that will die without getting the cure - and they are not getting it because the prices of the drugs are so extremely high. This is where FixHepC Buyers Club comes in. 

It is our mission to deliver life-saving Hepatitis C medicines to your doorstep for a negligible cost. We have set up a supply chain consisting of sofosbuvir production, packaging and distribution across the world. It is our hope this will bring down the Hepatitis C death toll under 100,000 and that in near future Hepatitis C death cases will be as few in number as possible with sofosbuvir-based medication. 

We strive to deliver generic Harvoni anywhere on the planet for less than $2,000 per treatment in about 2-3 weeks. With this prices, we could cure all Hepatitis C patients in the US for less than $7 billion. 

Are thing in Hepatitis C market likely to change?

Hardly. Pharmaceutical industry holds on to patents for drugs that last for 20- to 25-years. During this time, the prices of original Sovaldi and Harvoni will be extremely high, and Hepatitis C patients don't have 20 or more year to wait for patents to expire. 

If you have Hepatitis C, act now. The FixHepC Buyers Club will help you every step of the way, from getting the necessary medicines to monitoring your treatment success. You can call us or send us an email with your inquiries to This email address is being protected from spambots. You need JavaScript enabled to view it.

A short excerpt from a recently discovered audio recording of the Rev. Dr. Martin Luther King Jr. speaking at Syracuse University in July of 1965.

There are some things so dear, some things so precious, some things so eternally true that they're worth dying for. And if a man has not discovered something that he will die for, he isn't fit to live.

Tuesday, 12 January 2016 11:35

Hepatitis C Virus Life Cycle Video

Written by

Awesome animated video of HCV life cycle.

At FixHepC our goal is to see everyone, everywhere with Hepatitis C treated with affordable DAA medications so that no man, woman or child is left behind. The target is nothing less that sending this disease to the annals of history, as was done for smallpox.

Sounds impossible? Nothing is impossible (with the possible exception of breaking the Law's of Thermodynamics, but that's a different story, and the Big Bang Theory suggest maybe even that is possible).

First consider this:

And now consider what Lexus have just achieved:

The Lexus Hoverboard uses magnetic levitation to achieve amazing frictionless movement. Liquid nitrogen cooled superconductors and permanent magnets combine to allow Lexus to create the impossible.

Nothing is impossible - it may take a lot of work, by a lot of dedicated people - but hey, we've invented a Hoverboard and curing HCV is a simple willpower and logistics problem.

E = mc2

Everyone, everywhere = manufacturing * political clout * cooperative effort

Wednesday, 30 December 2015 06:15

PBS Listing - Some Tears In Heaven

Written by

They (who are they anyway) say, if it sounds too good to be true it probably is.

If you are GT1 or GT3 then the PBS looks like it is going to come through for you (and that is 90% of all patients), however if you're GT2 then your only option is Sofosbuvir +Ribavirin and if you're GT4 GT5 or GT6 then you're still looking at Interferon and Ribavirin + Sofosbuvir.

Here is the draft of the Australian HCV-DAA-Protocols that are in circulation and happened to appear in my email.

You can see what they mean for you using our beta Decision Support Tool - just put in your details to see what options are going to be offered (assuming there are no changes between now and then). At the moment the AASLD and EASL guidelines have not been added, but the PEG/Rib free option implements a subset of them.

Monday, 21 December 2015 11:52

PBS Listing - Almost Heaven

Written by

I don't have permission to attribute this but the source is impeccable:

Hi James

I think we should publicise the following key features of the PBS arrangement:

  1. All patients (>=18 years) with chronic hepatitis C will be able to access treatment through PBS. No restrictions based on liver disease stage or otherwise.
  2. The PBS is an uncapped program. There are no caps on number of patients who can access these treatments.
  3.  GPs will be able to prescribe following consultation with a specialist and community dispensing allowed.

The last point is something I am sure you will be pleased with. There apparently will not be an accreditation required, just an arrangement with a specialist clinician.

Kind regards

<Not John Denver>

Which is 100% awesome news.


And here is the Minister's Official Statement:

http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2015-ley154.htm

OMG they are serious, although there is a get out of payment free card:

Ms Ley said like access to all PBS medicines, funding was demand driven and the Government would account for any potential variations in spending accordingly. 

And here is the Official Fact Sheet

http://www.health.gov.au/internet/ministers/publishing.nsf/Content/FAE2B65331456243CA257F20006D4C48/$File/SL-154.pdf


And here is what the AMA say:

https://ama.com.au/ausmed/ley-tries-stymie-opposition-hep-c-link

Yes it will be paid for by the pathology cuts.....


And here is what Australian Doctor had to say about it:

Hepatitis C cures to be listed on the PBS

Alice Klein | 21 December, 2015 

The PBS listing of four new hepatitis C drugs will enable patients to clear the infection in as little as eight weeks, the Federal Government says.

The antivirals sofosbuvir (Sovaldi), sofosbuvir and ledipasvir (Harvoni), daclatasvir (Daklinza), and ribavirin (Ibavyr), which cost as much as $100,000 for a full course of treatment on the private market, will be made available through the PBS on 1 March 2016.

Combinations of the new-generation antivirals will be used to target the six different genotypes of hepatitis C, with the cure rate expected to be more than 90%. 

"With this announcement, there is great hope we can not only halt the spread of this deadly infectious virus, but eradicate it altogether in time," Health Minister Sussan Ley said on Sunday. 

GPs will be able to prescribe the four hepatitis C drugs in, or following, consultation with a specialist, according to a factsheet published by the minister's office.

All hepatitis C patients will be eligible for the drugs on the clinical advice of their treating doctors.

A spokesperson told Australian Doctor that GPs will be able to consult with a specialist by phone, mail, email or videoconference.  

The new treatments are better tolerated and require shorter durations than existing therapies, he said.

Treatment times range from 8 to 24 weeks depending on the hepatitis C genotype, the drug used and the patient's treatment history. 

Because the prevalence of hepatitis C is markedly higher in prisons, the new antivirals will also be made available to prisoners through the PBS, even though their healthcare costs are usually the responsibility of state and territory governments. 

Hepatitis Australia has welcomed the news, with CEO Helen Tyrrell calling it a "watershed" for the 230,000 Australians living with the disease. 

"So many people have been anxiously waiting for this announcement. This is wonderful news and it is such a relief to have an end to the uncertainty," she said. 

However, some doctors are unhappy that the $1 billion funding for the new hepatitis C drugs has come at the expense of funds being redirected from other health services. 

Ms Ley has confirmed that budget cuts to pathology and radiology announced last week as part of the mid-year economic and fiscal outlook were made so the government could fund the hepatitis C treatments. 

The AMA said it was wrong to cut funding for pathology and diagnostic imaging in order to fund one specific treatment. 

"They shouldn't be using patients to justify these funding cuts," AMA President Professor Brian Owler told News Corp. 

"I don't think there is a place for moral debate in health policy. As doctors we treat everyone, it's not about having a debate about more deserving citizens than others."

I'm writing this to help people understand what the recent announcement that DAA medications for HCV will be listed on the PBS. Here are a couple of links to it, both with interviews with the minister:

http://www.smh.com.au/federal-politics/political-news/turnbull-government-to-spend-1-billion-on-hepatitis-c-miracle-cures-for-all-20151219-glrib0.html

http://www.9news.com.au/health/2015/12/20/08/14/federal-government-to-spend-1b-to-subsidise-breakthrough-hepatitis-c-cures 

First let me say I think it's fantastic that the government has committed to listing these medications because it will make them more available.

You go girl!

The questions on everyone's mind, including mine, are "How much more available?" and "When?"

If you like executive summaries the answer is "We just don't know". We don't know because the key listing documents are not public and they are what will define access. The waiting is not yet over.

What follows might best be regarded as an informed guesstimate.

I have heard rumours on the grapevine like:

  • DAA prices ranging from $15,000-25,000 per patient,
  • 24 weeks treatment for the same price as 12,
  • Free medication for retreatment, and
  • A payment cap in that if enough patients present for treatment all the patients over the cap have their medications provided free (not all that hard given a production cost of $150 per patient).

So you could get all excited and think, hey, wow, if all that is true and the government spends a billion next year and that gets 66,666 treated and the overflow patients are free!

How good would that be? Too good to be true I expect.

Before you get too excited remember that the minister said $1 billion, and within a generation along with the "everyone will be able to have treatment".

She did not say "everyone will get treatment next March" and that would be practically impossible due to all the access bottlenecks.

A friend of mine told me, "If you really want to know what's going on then follow the money" and as luck would have it.....

Ms Ley said the PBS funding had been accounted for as part of Tuesday’s MYEFO, but was not announced until today due to confidential pricing negotiations with medicine suppliers

Hmm, never heard of a MYEFO but let's find it, trawl through it, and see what we can find. Ah ha, here it is:

http://www.budget.gov.au/2015-16/content/myefo/html/11_appendix_a_expense.htm

Scroll down to the Health portfolio and you can read:

Pharmaceutical Benefits Scheme   2015/16 $m  2016/17 $m 2017/18 $m  2018/19 $m
— new and amended listings 112.1 150.7 165.6 181.8

 So given the minister said the expenditure had already been accounted for in the MYEFO, the $1 billion appears to represent spending over the next 6 years.

Assuming that the $15,000 cost per patient is correct (and this would be 3-4 times better than anyone else in the Western World has negotiated) we could estimate the treatment targets as:

Year Spending Patients
2015/16  112,100,000  7,473
2016/17  150,700,000  10,046
2017/18  165,600,000  11,040
2018/19  181,800,000  12,120
2019/20  200,000,000*  13,333
2020/21  220,000,000*  14,666

* Estimated based on the 10% rise we see between 2016/17 2017/18 2018/19

For your interest I've included an Excel spreadsheet that allows you to play with various scenarios around cost, spending and infection rates.

For everyone to have access our government needs to have pulled a rabbit out of the had and negotiated a payment cap. I really hope they have, and that when the medications are listed they are routine Authority items (so any GP could prescribe them), not S100 (meaning only a limited number of specialists could prescribe them).

For anyone who has paid for medications that have not yet been delivered, and would now like to wait and see, we will be happy to refund your money.

 

HYDERABAD, DEC 8:  Generic pharmaceutical company Hetero today announced that it has received the approval for the fixed-dose combination Ledipasvir-Sofosbuvir (90mg/400mg) from the Drug Controller General of India (DCGI).

The drug, Ledisof, is a generic version of Gilead Sciences’ brand Harvoni which is approved by the US FDA.

The Hyderabad based Hetero had signed a non-exclusive licensing agreement with Gilead in September last year to manufacture and market the drug indicated for the treatment of chronic hepatitis C and is the first company to receive DCGI approval for this category of drug.

"We are happy to extend the fixed dose combination therapy Ledipasvir sofosbuvir (Ledisof) to Indian patients which is much more effective than Sofosbuvir," B P S Reddy, Chairman and Managing Director of Hetero said in a release issued here on Monday.

We expect approval for other Indian generics manufacturers to follow soon.

Saturday, 05 December 2015 02:46

A New Plan for PBS Pricing Negotiations

Written by

An open letter to all members of Australian Cabinet

If current medication pricing trends are allowed to continue then, when we finally invent a cure for cancer, you can almost guarantee it will be too expensive for all but the super rich to afford.

Take the new Hepatitis C medication Sofosbuvir as an example. The sponsor – Gilead Sciences – is, according to Bloomberg, demanding $1000 a tablet for it, making the monthly price $30,000 and the total price $84,000 for a full 12 week course. With 233,000 Australians having Hepatitis C, a 95% cure rate, and an annual death rate three times that of cervical cancer,  there is little doubt securing affordable access is an important issue.

The Australian Pharmaceutical Benefits Scheme (PBS) is the system we have to make expensive medications affordable. It does this by paying a subsidy to the manufacturers so that the maximum patient monthly price is $37 even if that medication costs $30,000 a month. In a case like this the PBS would chip in $29,963 to assist a patient to pay the manufacturer’s eye watering price.

Gilead sell Sofosbuvir for $10 a tablet in Egypt, so we are being asked to pay 100 times more and pricing negotiations have been stalled since 2014. Gilead has already made over $10,000,0000,0000 in profits from a drug that is documented to have cost less than $375 million to develop and $1 a tablet to make.

The scale of the problem is staggering. Worldwide, although over 150 million people suffer from Hepatitis C, a mere ½ a million people have been treated. During this same time 1,500,000 people have died from lack of affordable access. In a tragedy of breathtaking proportions, by the time Gilead’s patent expires, 12 million people who could have been saved will be dead.

The PBS provides equitable access to medication for all Australians but the increasing prices being demanded by Big Pharma for new medications mean the PBS is rapidly becoming too expensive for us to afford. The TPP, if signed into law, may well entrench this problem permanently. For example to provide all  Australians needing Sofosbuvir with access would cost our country more than the entire current PBS budget.

I propose the PBS adopt a new model for setting the price at which it is willing to subsidise medications.

  1. First we find the lowest market price offered by the manufacturer in the world (eg $10 in Egypt for Sofosbuvir).
  2. Now we calculate a multiplier factor of four based on Australia’s per capita income ($40,000), divided by Egypt’s per capita income ($10,000).
  3. This multiplier is used to set the maximum price that the PBS will pay, so in this case that would be 4 x $10 = $40 – this directly represents our capacity to pay in a world market situation.
  4. Should the manufacturer not wish to accept this offer price Australia applies a Super Pharma Profits Tax of 100% to every dollar over the calculated fair market price leaving the manufacturer free to charge whatever they like, but clawing extortionate pricing back into consolidated revenue using an alternate mechanism.
  5. In addition we adopt New Zealand’s methodology of not seeking to list every medication on the PBS, instead only listing one or two solutions to the particular problem This simple strategy forces Big Pharma to compete on price to receive (and maintain) PBS listing.

We have plenty of scope to improve our negotiating. New Zealand pays 1/8 the price of Australia for our most common medications. Overall they pay less than half what we do while still enjoying similar health outcomes. It's already bad enough that the Kiwis beat us a rugby.....

It is time for Australia to take a firm and unequivocal stance on Pharmaceutical pricing and not allow sick Australians to be held to ransom by amoral corporations.

Currently we pay the 3rd highest prices for medications in the world.

We can, should, and need to do better.

Dr James Freeman

Founder

GP2U Telehealth

Footnote: You may be interested to know that the forecast when a cure for cancer has been invented it will be too expensive to afford has already come true. Gilead's new leukaemia/lymphoma drug (which like Sofosbuvir they simply purchased rather than developed) comes in with their trademark $84,000 price tag.

http://www.fiercebiotech.com/story/gilead-picks-blockbuster-fda-blood-cancer-approvals-idelalisib/2014-07-23 

 

A report released Tuesday by US Senators Ron Wyden and Charles Grassley claims that Gilead Sciences priced the hepatitis C treatments Sovaldi (sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) with the sole goal of maximising revenue. The report was based on an investigation of 20 000 pages of internal company documents, dozens of interviews with health care experts and data from Medicaid programmes in all 50 states and the District of Columbia.

You can read an overview here:

http://hepatitiscnewdrugs.blogspot.com.au/2015/12/sovaldi-investigation-finds-revenue.html

The report in full is available here

An executive summary is available here.

A timeline of events pertaining to Gilead, Sovaldi and Harvoni is available here

A glossary of terms pertaining to the investigation is available here

Letters from state Medicaid programs are available here

Sunday, 29 November 2015 21:43

You Can't Patent The Sun

Written by

In 1961, Polio Vaccine Inventor Jonas Salk explained his decision to make his invention freely available with the words "You can't patent the sun".

185,000,000 people are infected with Hepatitis C and since a cure was invented only 613,000 people have been treated - during the same time 1,500,000 have died.

To mark World AIDS day on 1st December we have made this short video. If you care please share.....

Sunday, 18 November 2012 08:30

You Don't Look Like A Junkie

Written by

You Don't Look Like A Junkie from Kate Brown on Vimeo.

Thursday, 12 November 2015 22:28

Pharma Scores Rap Drug Cover-Ups

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This is a screenshot of an article in the Australian today.

Here is a link to the full text of the study published in the British Medical Journal

http://bmjopen.bmj.com/content/5/11/e009758.full.pdf 

And topping the list is..... No prizes for guessing.

Tuesday, 10 November 2015 12:40

The Real Development Cost of Sofosbuvir

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So Big Pharma's argument about pricing goes like this:

We spend a lot on R&D so we need to make a lot back when we find a winner.

Now with Pharmasset we can look at the balance sheet immediately prior to Gilead's purchase. At the time the sunk capital cost (accumulated deficit) was $324 million. That's a lot of money, but nothing like the $7 billion valuation in the market (20x) or the sale price of $11 billion (33x).

That $324 million represents almost the ENTIRE development cost of this medication. There would have been another $50 million for the Phase 3 trials. Call it $400 million all in.

With some 613,000 people treated to date at around $50,000 per person the return is already north of $30 billion. That is 60 x the sunk cost in 3 years.

To treat the entire US population would be north of $200 billion. That is 500 x the sunk cost.

I believe Big Pharma takes big risks and has a right to big profits. The investors in Pharmasset got a 20 x + return and took almost all the risk. That does not seem entirely unfair. Gilead on the other hand took very little risk and is already sitting on 3 x at the price of 185,000,000 of our fellow citizens of the world being unable to access treatment and 500,000 a year perishing of a treatable disease.

If we are happy to live in a world where the cure for cancer is invented but only the super rich can afford it then that's fine.

If however we want to live in a world where patient lives balance patent rights we probably need to start thinking about how we provision decent, but not indecent profits and pricing practices.

Wednesday, 04 November 2015 12:11

Houston, I think we have a problem....

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You've almost certainly seen a version of this picture. It's called earthrise and really hammers home the idea that we live co-operatively on a tiny speck in a dark black void.

This particular version was taken out of the window of Apollo 13 on its ill fated journey to the moon.

So, why is it here?

http://fixhepc.com/have-your-say-with-the-federal-government/252-buyers-club-scheduled-to-meet-key-decision-makers.html?start=18#2254

According to Reuters John Martin, CEO of Gilead Sciences, has taken home $400.6 million dollars between 2009-2013 and is on track to take home $600 million making him the best remunerated executive in the USA.

Since HCV DAA medications became available 500,000 people have been treated, 1,500,000 people have died and 150,000,000 remain infected.

At that rate, this week one man will take home over $2 million based on profits from HCV medications while 10,000 fellow citizens of the world will die due to lack of access to those medications.

I don't know about you, but to me, there is something not quite right about these numbers.

I wonder what sort of world we would be living in if the companies behind penicillin and polio vaccine had behaved in the same way...

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