Hi Meg,

done, I updated the PDF in my previous post and I am uploading it again here:



Thank you for having made the Portuguese translation, I enjoyed learning couple of Portuguese words.

Regards,
RHF

Hi Meg,

I do not speak Portuguese, yet with some Google Translate support, I was able to include your text into a bilingual PDf file, PT-EN.
Please have a look on it. In case you notice any error, please let me know and I will fix it.



Regards,
RHF

Powerpoint in french



and illustrated presentation, useful to have the pics in the text, but sorry the mise en page isn't as perfect as I'd have liked.



recording tomorrow...

Now I've corrected the last typing errors, and tidied up the sub-headings; this really is the Final Version !

Recording on tuesday or wednesday next week.

Salut à tous et toutes !!!
xxx

Here is the french version corrected; I have credited Dr Michel Busch for the translation.
We will be recording him reading it sometime next week for the voice-over: do you have geeks your end to edit it in to the video?
Or do you prefer we do it this end before uploading somewhere? (I have a youtube channel I could leave it on, for ex, if this is your favourite option). Please advise.

Very best wishes,
suzy



Lets now see if I can make the file stick to the message...

thanks for the pdf, I've forwarded it to a french dr friend for checking & will re- post the tweaked version asap, also will try the ppt presentation now I've got the hang but my software is old (office97).
Do you have someone doing subtitles or overdubbing on the youtube vid?
I could record my dr friend reading the french transcription, for example, and send as mp3 ( or other format)...well I think I could...let me know if its useful, I like to help get it out.
very best
suzy

french? here...its not ppt, its word (.doc)

great stuff, thank you xxx

I am so sorry for being too late.

I have been too busy last week.

Attached is korean translated version.

I also uploaded this pdf on korean hep-c forum.

Thank you for your wonderful work, Dr. Freeman.

Hello Everybody,

because the presentation of dr. Freeman at the EASL ILC Congress was followed by a press release on the ILC congress website (ilc-congress.eu/low-cost-generic-direct-...randed-formulations/) I enjoyed doing an additional translation for the press release.
The attached document is made blingual (Romanian - English).



BR
RHF

Hello Gaj and Klhilde,

thank you for your replies, it does contain couple of information it worth thinking on it.
Yes, spammers, people trying to sell things, etc. are part of the real life. Also managing websites in various languages is quite a challenge. But this would be too BIG for the moment.

The idea proposed would be to proceed in small steps (or at least as big as it can be managed) having the following issues in mind:

Issue1: using the automated translation option does not allow (afaik) search engines to index websites. This means if someone looks for a keyword in another language than English, most probably will not reach fixhepc.com.
Issue2: indeed, translations made by translation engines are .....funny...(let's use this word for the moment).
Issue3: human translation means skills&time&effort that not so many people have available.
Issue4: trying to reinvent the wheel (like create a new forum somewhere) and doing something BIG in short time most probably will lead to failure.
Issue5: spammers, faulty translations, etc. can invalidate the initial goal.
Issue6: I was extremely surprised that since 16th of April until today, I could find only 1 website in RO who published an English article related to the EASL presentation made by Dr. Freeman in Barcelona. I could not find any other website or publication in RO to at least instruct people that there are HCV news on the horizon....coming from Australia.

Looking at all these from above, the situation looks depressing. This is the point to have in mind the old saying "A little stone in the way overturns a great wain." and thinking "What if a small effort can have a butterfly effect?"
e.g.:
- invest 30 minutes to voluntarily translate a text being not very long (for instance a press release) from English to the native language. Make sure to always indicate the source of information and/or if possible make a bilingual document. (see the file attached for instance)

- invest 15 minutes to make sure the translation is not faulty. (Garbage text will will end in the trash can)
- invest 5 minutes to create a post on the fixhepc forum using 2 titles: the English title of the text and the title translated in the native language (hopefully search engines will find them both) and upload the translation (perhaps as PDF file as it would enable the easy share of information).
- invest 10 minutes to announce interested forums in the homeland about the translated text being available in the native language.

---

Total time invested : 1h
If such a post will be read in the homeland by at least couple of people, it will be in any case a step forward.

I am aware this idea is not perfect and that it can be further improved. Yet, by simply put it into practice it might turn into a small contribution that could help other people.

Thinking on my story, I managed to find out about fixhepc just because an european doctor (not from RO) told me that I could be cured with Harvoni. This small piece of information, "Harvoni", was the trigger for me to find out about India, Greg Jefferys, fixhepc. What if such "small pieces" of information like a simple press release translated in the native language might trigger others to find&get help.

Sorry for the long post,

BR
RHF

Hello Everybody,

@Dr. Freeman: thank you for the PPT presentation from the ILC EASL 2016 congress.
I attached to this topic the Romanian translation: one PDF file with Romanian text only and one PDF file conceived as bilingual document RO-EN.

---

@Dr. Freeman: multumim pentru prezentarea PPT de la congresul ILC EASL 2016.
Atasez acestui topic traducerea in limba romana, un fisier PDF doar cu textul in limba romana si un fisier PDF conceput ca document bilingv RO-EN.

If you have a look at the map in the EASL presentation you will notice that patient density essentially relates to "English speaking" countries.

If you speak English as a second language converting the attached presentation into your native language, and adding a "translated by X X" comment would make this information far more widely available, particularly if the translated versions were then posted on the native language Hep C forums around the world (probably as PDF rather than PPTx because it's easier to read it on any device).

If you have the skills, your translation might be the most important 1 hours work you ever do in terms of global impact.

Here's my notes for the presentation and the presentation as a PDF and PPTx






And here I am giving the presentation with my eyes closed!





--- Title
REDEMPTION-1 is an ongoing open label study assessing the safety and effectiveness of generic direct acting antiviral Hepatitis C medication. This is an interim analysis of the all results available to date.

--- A Global Tragedy
Hepatitis C, Hepatitis B, HIV, TB and Malaria are the 5 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.

Across the world 150 million people are infected with Hep C and it causes over ½ a million deaths each year, 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.

It is sobering to reflect that more patients died last year than received the new treatments.

--- The Deployment Problem Is Price
The deployment problem is price.

Although the ingredients for a 12 week course of Sovaldi cost less than $100, the US retail price is a $84,000

To put that price in perspective if Apple put the same 100,000% markup on a new iPhone it would cost $1 million dollars.

--- Background
So the staggering prices of these new medications prevent patient access to safe and highly effective treatment.

But… Generic versions are being mass produced for under 1% of the current US retail price, in countries where the patents have been rejected.

And… Under the laws of Australia, the UK, and many other countries, individuals have the right to import a three month supply of medication, for their personal use

--- The Legal Basis Of Personal Importation
Patents provision monopoly rights that are open to abuse, however other laws provision other rights.

Article 60 of the World Trade Organization TRIPS agreement makes small consignments exempt, and in line with Article 60 most countries allow some form of personal medication importation.

The fixhepc website was set up to help patients safely access generic medication and the forum there has over 1000 patients discussing their generic treatment experiences in real time.

--- Methods
When the first patient asked for help, stating he was going to import generics with or without me, I concluded I could improve his safety if the medications he sourced were shipped to me first for testing. The deal was if they passed testing he could take them, and if not they were going in the garbage. The medications tested correctly, the patient took them, and he’s now past SVR24 and cured.

That single patient might have been my only patient, but the news leaked and 1 became a dozen, who in turn became hundreds. Thus was born REDEMPTION.

Consecutive patients were enrolled and assessed pre-treatment, during treatment and then for SVR

The objective was to answer the two key clinical questions – do generics work? and are they safe?

--- Sofosbuvir NMR
For interest here is an NMR spectrum of some generic sofosbuvir. NMR is one of a range of techniques, such as High Performance Liquid Chromatography, Mass Spectrometry and X-ray crystallography that can establish the precise nature and purity of a medication.

--- Over 400 Patients Worldwide
Although REDEMPTION is based in Australia the gp2u Telemedicine platform allowed patients from around the world to enroll

--- Baseline Characteristics
On the right you can see the genotype breakdown with the majority genotype 1, just under 1/3 genotype 3 with smaller percentages of the other genotypes.

448 patients enrolled.

There is a roughly 50:50 split between SOF+LDV and SOF+DCV with just over 10% also using ribavirin

This is a relatively unwell cohort with nearly 50% treatment experienced, over 30% cirrhotic, and a significant number who had previously been rejected from at least one clinical trial.

There was a slight male bias, an average age of 54 and a mean viral load of 2.8 million

--- Viral Response
Let’s look at the on treatment viral kinetics The scatter plot dots are the viral load at various time points, and the size represents the log number of patients. Blue is Ledipasvir and Pink is Daclatasvir.

Unlike the usual reporting which stops at < LLOQ (<15) we have differentiated < LLOD as another data point and I think this makes evident a 2 stage kinetic decay – the first stage is rapid, but the second is substantially slower and it’s this slower second stage that dictates the minimum treatment duration.

The 3 grey lines are from data published in the Lancet in 2014 about the on treatment kinetics for SOF+PEG+RBV. As you can see the response for both the generic combinations used was substantially faster than this demonstrating the impact of effective NS5A inhibition. The difference between the SOF+LDV and SOF+DCV kinetics, where Daclatasvir looks slower, is an artifact due to it’s higher use in GT3 where the kinetics are slower than in GT1. If we look only at GT1 with SOF+DCV we see the response is slightly better that SOF+DCV and it crosses <LLOQ a little earlier.

There was one virological breakthrough.

--- SOF+LDV+RBV for GT3?
So now to the first of the results.

In 2015 Professor Ed Gane published an interesting study about the use of SOF+LDV+/-RBV in GT3

One group – treatment naïve patients who also had RBV did very well with a 100% (26/26) SVR rate.

We’ve duplicated that result with generics suggesting it is repeatable and should perhaps be investigated at a larger scale.

--- REDEMPTION-1 HCV RNA < LLOQ
Here we can see that at the end of treatment 99.6% of patients were <LLOQ. One virological breakthrough reduced the result for LDV

The overall SVR4 rate was 94.4%.

Looking at GT1 only the results of LDV and DCV were similar, with the LDV result again suffering from that breakthrough patient (S282T RAV)

--- Published SVR12 Results
Dr Andrew Hill and his research student Anna Savage aggregated all the clinical trials data we could find for the DAA combinations SOF+LDV and SOF+DCV, and they are presented here.

And if we compare this to the results of generics…

--- REDEMPTION-1 Overall SVR4 Results
We don’t see a lot of difference.

The 100% results in GT2,4,5,6 are of course pretty meaningless given the tiny numbers, but for GT1 and GT3 the results are in line with expectations.

We do expect a handful of patients who passed SVR4 to fail SVR12 but don’t expect that to cause a huge change.

--- Patient Safety
No new or unknown side effects were reported with headache, fatigue and insomnia being the most common

3 patients with compensated cirrhosis temporarily decompensated on treatment initiation but continued with treatment

4 patients who enrolled have since died, all from HCC

--- Summary
So in this interim analysis treatment with legally imported generic DAAs produced similar SVR rates to what we would expect from the clinical trials of their branded counterparts.

Doctors prescribing and monitoring patients taking generics can take comfort from the fact that, like the HIV generics that came before them, HCV generics deliver robust clinical results.

--- Conclusions
Generic cure for Hepatitis C is available now for $1000 and works as expected

Given current production costs, $200/patient treatment with SOF+DCV is possible, not in the future, but right now

It’s sad to reflect that at a price of $200/patient the entire world – all 150 million patients - could have been treated for less than the $31.5 billion dollars in profits made from the Sovaldi franchise in the last 3 years.

Without treatment the future for millions of patients infected with HCV looks like this…

--- RIP

Today over 1000 of our fellow citizens will die from a disease we have the power to cure.

We have the power to FixHepC.

The real question is do we have the will power? The will power to think global, but act local, and see cure deployed on a mass scale?

Generics work. Let’s deploy them and wipe Hepatitis C off the face of the planet, just like we’ve done with smallpox and polio.

Twinvir launched on the 27th August 2015, so there are patients past SVR4 but not SVR12. The first SVR12 results will appear in mid March.

My first patients started on it mid November. All were viral load zero within 4 weeks.

Prior to using it we tested Twinvir at the NATA accredited National Measurement Institute. If you search the certification documents for Sofosbuvir and Ledipasvir for the word Twinvir you will see that testing noted. You can find those certification reports here:

fixhepc.com/blog/item/16-testing-provisions-patient-safety.html

We did RVR testing on Twinvir during the period 20-28 November and observed excellent clinical effects with the worst 1 week viral load drop being 1,200,000 -> 636 (F3), the best being 2 million to undetected.

If you read the TGA submission here:

www.tga.gov.au/file/8444/download

You will find it stated that:

Ledipasvir is practically insoluble (<0.1 mg/mL) across the pH range of 3.0-7.5 and is slightly soluble below pH 2.3 (1.1 mg/mL). The partition coefficient (log P) for ledipasvir is 3.8 and the pKa1 is 4.0 and pKa2 is 5.0.

This is why you must have stomach acidity to absorb it - without that it won't dissolve well. Once it is dissolved it's not in a crystalline form and will be absorbed. The normal volume of the stomach fluid is 20 to 100 mL and the pH is acidic (1.5 to 3.5) so I'm actually quite surprised it is not without food (to increase the acidity) but as you will read in the auspar document it still gets absorbed in the presence of food.

If you read Gilead's submission to the European Medicines Agency here:

www.ema.europa.eu/docs/en_GB/document_li...3850/WC500177996.pdf

On page 8 you will find Gilead stating:

Three crystalline forms are known and ledipasvir acetone solvate is the designated commercial form. The first step for finished product manufacture involves the dissolution of ledipasvir in ethanol followed by spray-drying and thus precise control of morphology and particle size is not considered important.

Ledipasvir acetone is what Twinvir uses.

On the topic of crystalline forms most people don't know that Gilead tested crystalline Form-I Sofosbuvir but substituted Form-II in the commercial product. See page 12 here, and note that the AUC data in the commercial product is inferior to what was trailed.....

www.tga.gov.au/file/6066/download

We will be publishing generic SVR results at EASL if our abstract is accepted. The are no nasty surprises in it.

Hi Everyone

Went over to the Russian site to say g'day to our heper friends. Modern technology allows us to translate the site which does cross over quite well. Anyway Alex the administrator of the site responded and I thought I'd share. I've seen some Russian inquiry on the shoutbox/public chat and think we should be translating so that we can put them in touch with our friends over there and cc Nadia in on the conversation. Better check that this is okay with Nadia first, I guess:

Hi, Emilio!

I'm Alex, the administrator of several sites on the subject of hepatitis C in Russia. The oldest of them - HCV.RU (information portal and a great forum for patients, doctors, relatives, etc.) has about 15 years.

I saw your greeting message on the new forum GCFORUM.INFO and decided to contact you.
This forum is open due to the fact that in Russia, trade with Chinese medicines in general is a criminal offense.
So we have more fun than you ...
Because forum is open as domain .ihfo, on US hosting.

The site HCV.RU collected gigabytes date information on diagnosis and treatment of hepatitis C, according to the latest drugs, treatment regimens, etc. I'm going for many years.

Thus, if your forum will come some Russian-speaking people - you can send them to us!
And we will send you all of our English-speaking. : –)
By the way, we have a lot of information in English.
Eg: www.hcv.ru/files/easl-recommendations-2015-summary.pdf

Sincerely,
Alexey Koshcheev

www.hcv.ru/
www.gepatit-c.ru/
gepatitnews.ru/
gcforum.info/