TOPIC:

And a link to the article Splitdog was quoting.

regist2.virology-education.com/2016/12co...ion/21_Sulkowski.pdf

Thanks Splitdog, great idea (and article). I think there will be a few GT3s watching this with particular interest.

Here is some further info on thirteen clinical trials involving Vox that I have been able to track down. I've included trial numbers for all phases for completeness but only a shortcut to Phase 3 which are the ones of most interest to us as they determine approvals. The four phase 3 trials are called Polaris 1 - 4.

Phase 1 completed: NCT02402452, NCT02533427, NCT02397707, NCT02185794

Phase 2 completed: NCT02378935, NCT02378961, NCT02202980, NCT02536313

Phase 2 active(recruiting): NCT02745535

Phase 3 active(not recruiting): NCT02607735, NCT02639338, NCT02607800, NCT02639247

clinicaltrials.gov/ct2/results?term=Gs-9...rcv_e=&lup_s=&lup_e=

More good info:

www.hepatitisc.uw.edu/pdf/treatment-infe...e-3/core-concept/all

And a bit of 'light' reading for those who are interested.

hepatitiscnewdrugresearch.com/sofosbuvir...vir-and-gs-9857.html

"Come on Vox!"

Yes, come on you Vox

SOF+VEL+VOX will be Gilead's answer for relapsed patients. Hope it can be approved soon

Me, too!

October 20, 2016

www.gilead.com/news/press-releases/2016/...hcvinfected-patients

Hi

From the waiting room
Geno 2b Apparently since a blood transfusion and subsequent yellow Jaundice in 1963
Diagnosed in1991 failed a 24 week ribavirin/Peginterferon course
2015 started on course of Sof/rib after many problems
2016 failed the Sof/Riba course after 12 weeks
Complete relapse.
Awaiting lab test reports on type of mutation.
Hope the new sof/vel/vox will be applicable. It looks promising.
I am being told that the new thinking is virus mutates after completion of meds and have to wait before starting next course,
Are there any planned fixhepc trials with Vox?
TTL

Hi TTL,

Sorry to hear that your previous treatments failed you. Fortunately there are now better options available or in the pipeline. Voxilaprevir in combination with Sof/Vel is one that does look promising for the future per this thread fixhepc.com/forum/relapse-corner/1263-vo...inhibitor.html#22461

I'm not an expert but you don't appear to have treated with a NS5a combination, just with Sof/Riba? If that is the case and assuming you don't have a Sofosbuvir resistance (extremely unusual) there may well be current options that would be effective for a genotype 2b patient without needing to wait for Vox to become available such as Sof/Daclatasvir or Sof/Velpatasvir. If you can provide a bit more information about how soon after finishing treatment you relapsed and what your fibrosis levels are that may assist others to comment.

Vox is not available as a generic yet, but your SVR rate with either Sofosbuvir + Daclatasvir or Sofosbuvir + Velpatasvir will be >95%

Yes, you may not need voxilaprevir. Sofosbuvir (an ns5b inhibitor) creates temporary resistance s282t that gets cleared by itself in 6-12 months. onlinelibrary.wiley.com/doi/10.1111/jvh.12405/summary There are also L159F and V321A, but those were found to be weak and to not influence treatment outcomes greatly.
jid.oxfordjournals.org/content/early/2015/11/24/infdis.jiv564
In contrast, Ns5a inhibitors create permanent resistance.
Yes, you should wait for lab tests for resistance to see if you have any baseline RAVs, except possible ribavirin resistance.
www.ncbi.nlm.nih.gov/pmc/articles/PMC3961994/
www.ncbi.nlm.nih.gov/pmc/articles/PMC4786064/
www.nejm.org/doi/full/10.1056/NEJMoa1512612#t=article
Resistance profile of velpatasvir looks slightly better then the one of daclatasvir for gen 2 viruses. (According to the articles above).
The choice between vel and dac, of treatment duration and whether to include ribavirin for the third time is a really important one and depends on your fibrosis state and baseline RAVs. The addition of vox vs using ribavirin for the third time, if needed, also depends. You should research it very carefully. Vox may be not necessary and would possibly bring in NS3 resistance, if failed.
The outlook for you is very good though, if treated properly (and timely).

Gilead announces SVR12 Rates From Four Phase 3 Studies of sofosbuvir + velpatasvir + voxilaprevir! (20 October 2016)
Filing FDA application very soon.
www.gilead.com/news/press-releases/2016/...hcvinfected-patients
www.empr.com/idweek-2016--adult-infectio...-hcv/article/566893/

The most common prior NS5A inhibitors were ledipasvir (55 percent) and daclatasvir (23 percent).

Complete results from all four studies will be presented at the AASLD Liver Meeting® 2016 in Boston. Nov 11 - 15, 2016.
www.pr-medicalevents.com/congress/aasld-2016/