TOPIC:

vitrus wrote: It has gastrointestinal side effects

Citation please?


Also, Sofosbuvir has a different mechanism of action to both Vel and Vox which themselves have differing mechanisms. As such it is always used in combination with these or other drugs so talk of "sof failures" and "sof relapsers" needs to be qualified by what it was used in combination with (and the genotype and fibrosis status involved) as failure or relapse is far, far more likely to relate to one of those factors than Sofosbuvir.

The data is preliminary (from Stage 2 trials), but Gilead announced that sof/vel/vox is 99% effective for previous DAA failures of the studied classes (without naming the classes).
Source: GILEAD announcement on EASL Conference in April. It is also widely known that vox causes diarhea and is otherwise bad for your stomach in the short term. (See links below).
The data is from Stage 2 trials. So for retreatment of DAA-failures vox is a much much more effective option than say vel+sof for 24 weeks or with ribavirin. Vel is not good for retreament. It is recommended for treatment-naive people. Because it has almost no side effects and although there's no data yet if sof/vel/vox is effective for sof/vel relapsers, it is likely that this data is going to be available in the beginning of 2017.
If sof/vel/vox indeed proves effective against vel-resistant viruses, there's more probability to get cured if you do, say, sof+vel and if it doesn't work you do sof/vel/vox. Because sof/vel won't bring in any NS3 mutations and there's no data on retreatment of sof/vel/vox failures yet.
That said, if you're treatment-naive, get sof/vel. If DAA-experienced, wait a little. No data on if vox would help and in what situations it would (after which treatment regimens, in which liver conditions), but Stage 2 shows it is effective.
regist2.virology-education.com/2016/12co...ion/21_Sulkowski.pdf
www.natap.org/2016/EASL/EASL_31.htm

The problem is though, vox is not going to be available until mid-2017. It is effective in cirhotic populations.

hi vitrus,

"It is also widely known that vox causes diarhea and is otherwise bad for your stomach in the short term.(See links below)"

Again, citation please? There is nothing about adverse events relating to voxilaprevir in your claimed "links below".

(And no, telling me to go and Google it doesn't work. You are the one making these claims. Please back them up with some evidence.)

I Agree
natap.org/2016/EASL/EASL_10.htm
www.gilead.com/news/press-releases/2016/...epatitis-c-therapies
The last slide

Nausea plus diarhea vs no sides for vel.
But those are mild compared to ribavirin-related side effects. And the stomach usually recovers quickly.

Slides also show it's a stage 2 trial with small numbers for each combination. But 127/128 people were cured. So we'll have more certainty in January.

Sofosvel needs to be tested by someone who is not the drug producer, like it was done for Twinvir.
Otherwise, personally I'm waiting for the Drug Controller General of India approval. They might ask for local trials though.

Because I need a permanent record of this statement.

MonkMed wrote: UPDATE: July 27th 2016

As per the current timelines GILEAD Licensed Velpatasvir will be available in early September 2016 in India. Epclusa( GILEAD Velpatasvir) is already licensed to Gilead’s 11 Indian manufacturing partners which includes top brands like Mylan,Cipla & Natco which have undergone a complete transfer of technology(TOT). en.wikipedia.org/wiki/Technology_transfer.

Licensing does not mean just a business aspect of royalty sharing but more importantly ensuring the quality of the licensed product is exactly same as that of the original pill. This aspect is ensured by rigorous TOT which is explained below.

A complete technology of transfer(TOT) means the process of manufacturing of the pills is exact same as of the original GILEAD pill not just limited to the API but aspects of Excipient which is the NON API materials that goes into the manufacturing en.wikipedia.org/wiki/Excipient.

On top of the above, premium companies like Cipla and Mylan have their own Quality assurance processes. So even if pills are manufactured by Hetero and Hetero has its own Quality Assurance and Testing of the pills, after they hand over the pills Cipla and Mylan have their own comprehensive Quality Assurance and Testing process . We like this aspect of double testing which is the precise reason doctors world over trust Cipla and Mylan.

Mylan has grown from the third-largest generic and pharmaceuticals company in the United States to the second-largest generic and specialty pharmaceuticals company in the world.en.wikipedia.org/wiki/Mylan.

On top of all the above all Indian manufacturing units that manufacture or sell Licensed products are US FDA certified and have to keep up with rigorous standards also called Current Good Manufacturing Practices (CGMPs)

www.fda.gov/Drugs/DevelopmentApprovalPro...turing/ucm169105.htm

Currently DCGI (Drug Controller General of India) approval for generic Velpatasvir is in process as the 11 Indian companies are gearing up production for early September launch.

What I gleaned from this is Sof/Vel is way better at treating people with RAV's than say Sof/Dac. So it would be better for relapsers. However, I am still going to wait for the silver bullet, Vox.

Doesn't it say in there somewhere about SVR12 >90% of DAA failed treatment?

vitrus wrote: I Agree
natap.org/2016/EASL/EASL_10.htm
www.gilead.com/news/press-releases/2016/...epatitis-c-therapies
The last slide

Nausea plus diarhea vs no sides for vel.
But those are mild compared to ribavirin-related side effects. And the stomach usually recovers quickly.

Slides also show it's a stage 2 trial with small numbers for each combination. But 127/128 people were cured. So we'll have more certainty in January.

Thanks,

Yes, early trial, small cohort and no placebo.

I went and had a quick look at just the diarrhoea results for Vox trials I could quickly access and the figures are all over the place. NCT02378935 was 9.6%, NC02378961 was 22.7% Both were non placebo trials. Interestingly I found an (admittedly phase 1) trial that used placebos NCT02185794. The placebo arm had 12.5% whereas the drug arm was only 5%.
The problem with quoting small scale trials which contain no placebo arm like you did is that anytime that you get a group of people together for a period of say 12 weeks and ask them to report adverse events, diarrhoea and nausea are going to show up fairly regularly whether those people have HCV or not and whether they are taking drugs, placebo or nothing at all. They are really common symptoms of everyday life that vary from location to location and season to season so you do need to be extremely cautious about attaching significance to them particularly if there is no placebo arm to the trial.

I would also suggest you reconsider your "no sides for vel" statement. See p91 (onwards) below which shows them plus whether they were considered relevant. This is why we need placebo arms, to determine whether reported sides are related to the drugs or coincidental.

www.ema.europa.eu/docs/en_GB/document_li...4210/WC500211152.pdf

And as splitdog notes above the Velpatasvir/Sofosbuvir combination is quite an effective and recommended retreatment course for many relapsers. More info here www.hepatitisc.uw.edu/pdf/treatment-infe...e-3/core-concept/all

However it is less effective with "hard to treat" patients such as GT3a relapsers particularly where they have high fibrosis levels or cirrhosis which was why we were discussing the use of Voxilaprevir as one option even though it entails a wait.

vitrus wrote: Sofosvel needs to be tested by someone who is not the drug producer, like it was done for Twinvir.
Otherwise, personally I'm waiting for the Drug Controller General of India approval. They might ask for local trials though.

Perhaps the question you should ask is "Has anyone other than the manufacturer tested Sofosvel and if so what was their finding?"


PS Welcome, I'm not always this grumpy and I wish you well for a swift resolution of your choice of treatment and success with it.

Has anyone tested sofosvel for solubility and manufacturing process quality?

All I could find was www.facebook.com/sofosvel/photos/pcb.157...9006/?type=3&theater

Another point is. We might get sof/vel in India in September. There may also be a delay because Indian law requires local trials to be held in India, unless negotiations to waive the requirement succeed. The expected delay is 0 days to 6 months.

Can anyone give me a ballpark figure for shipping to Vancouver BC? I'm trying to put together information for people who contact HepCBC about getting treated. I'd like to be able to tell them how much 12 weeks of Harvoni equiv will cost them. I see the $1600 US price for the drugs but can't figure out how much the Fedex courier costs.

CD

The drugs are $840. Shipping for me in the US was $90. 3 days.

Wow.. that is amazing. And the price you got was from the drugs in the trial and via Monkmed? I need to be sure ..The price listed in the Redemption trial says $1600 US (fixhepc.com/) "Affordable treatment for Hepatitis C is now available for $1600 via parallel importation of Sofosbuvir, Ledipasvir and Daclatasvir. These are active molecules that make up the new age Hepatitis C treatments Sovaldi (400mg sofosbuvir), Harvoni (90mg ledipasvir / 400mg sofosobuvir) and Daklinza (60mg daclatasvir)." or am I reading this wrong? Does this mean $1600 for all 3 drugs?

CD

$840 for the Sofosvel. You're in the Sofosvel thread. The other drugs are available through other channels, but I got mine directly from Beacon Pharmaceuticals. A script, a bank transfer, and they're on their way! From what I've been reading, (and I have read a lot ), Sof/Vel is the best option for treating ALL genotypes now.

Okay.. Right, I'm in the right thread. I'm cured now, and just trying to help others who are scared, poor and being denied treatment. Our organization HepCBC is totally for the Redemption trials. We are trying to gather as much info as possible so as to make the journey easier for those who come to us for advice. So please educate me: I thought that the fixhepc club had an arrangement with Monkmed for the trial, or is there also an arrangement with Beacon. I don't know and I'm not trying to cause trouble. We just need to know that if we send someone to the Redemption trial that they will get certified meds with guaranteed delivery. Is this the case for Beacon?

CD