Voxilaprevir (akaGS-9857) - A new Protease Inhibitor

This topic has 49 replies, 11 voices, and was last updated 7 years, 3 months ago by Dr James.

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26 August 2016 at 3:19 am #22533
Gaj
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- Guardian Angel
@gaj
And a link to the article Splitdog was quoting.

http://regist2.virology-education.com/2016/12coinfection/21_Sulkowski.pdf

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
26 August 2016 at 3:25 am #22535
Gaj
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- Guardian Angel
@gaj
Thanks Splitdog, great idea (and article). I think there will be a few GT3s watching this with particular interest.

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
27 August 2016 at 8:42 am #22565
Gaj
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- Guardian Angel
@gaj
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

https://clinicaltrials.gov/ct2/results?term=Gs-9857&recr=Closed&type=&rslt=&age_v=&gndr=&cond=&intr=&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&phase=2&rcv_s=&rcv_e=&lup_s=&lup_e=

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
28 August 2016 at 1:24 am #22574
splitdog
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- Guardian Angel
@splitdog
More good info:

http://www.hepatitisc.uw.edu/pdf/treatment-infection/treatment-genotype-3/core-concept/all

splitdog@roadrunner.com

Genotype 3
VL 4,100,000
ALT 101 AST 71
Treatment Naive
Started Sof/Dac Jan 12, 2016
VL= <15 4 weeks in. AST/ALT normal.
VL=UNDETECTED 8 weeks in.
SVR4= Virus back. 3,300,000

Started generic Epclusa Sep. 23, 2017

4 weeks in <15 *Detected.
12 weeks in <15 *Not Detected.
16 weeks in <15 *Not Detected.
Finished 24 weeks treatment 3-17-18
SVR5 <15 Not Detected.
SVR 20 <15 Not Detected.
SVR 44 <15 Not Detected.

Thank you Jesus.
Thank you Dr. James
28 August 2016 at 5:14 am #22577
Gaj
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- Guardian Angel
@gaj
And a bit of ‘light’ reading for those who are interested.

http://hepatitiscnewdrugresearch.com/sofosbuvir-velpatasvir-and-gs-9857.html

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
14 October 2016 at 11:22 pm #23853
splitdog
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- Guardian Angel
@splitdog
“Come on Vox!”

splitdog@roadrunner.com

Genotype 3
VL 4,100,000
ALT 101 AST 71
Treatment Naive
Started Sof/Dac Jan 12, 2016
VL= <15 4 weeks in. AST/ALT normal.
VL=UNDETECTED 8 weeks in.
SVR4= Virus back. 3,300,000

Started generic Epclusa Sep. 23, 2017

4 weeks in <15 *Detected.
12 weeks in <15 *Not Detected.
16 weeks in <15 *Not Detected.
Finished 24 weeks treatment 3-17-18
SVR5 <15 Not Detected.
SVR 20 <15 Not Detected.
SVR 44 <15 Not Detected.

Thank you Jesus.
Thank you Dr. James
15 October 2016 at 12:50 am #23860
LondonGirl
- Topics: 16
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- Guardian Angel
@londongirl
Yes, come on you Vox

GT1a Dec14 F2/8.7 VL 900000-2.5M
Jan16 Hepcivir-L MonkMed/Redemption
Baseline: VL 913575 Alt 76 Platelets low
Wk2 VL1157 Alt 23
DET Wk 8 VL 32 Alt19 ‘In the slow lane’
June16 Fibro 5.7 F0/1 LIF 1.5
Wk 11 VL<12 Alt 13 Det/Unq
Extending tx 12 wks Mylan Sofo/Dac MonkMed
Wk 14 VL <12 Det/Unq
Wk 16 VL UNDETECTED
Wk 22 + 4 Wks Sunprevir FixHepC
Wk 24 UNDETECTED Alt 13
Wk 12 post tx SVR12 Wk 26 SVR24
Thank-you Tim, Dr Debasis @ MonkMed & Dr Freeman @ Fix HepC
18 October 2016 at 7:04 am #23939
tweakmax
- Topics: 18
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- Guardian Angel
@tweakmax
SOF+VEL+VOX will be Gilead’s answer for relapsed patients. Hope it can be approved soon
18 October 2016 at 7:46 am #23940
splitdog
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- Guardian Angel
@splitdog
Me, too!

splitdog@roadrunner.com

Genotype 3
VL 4,100,000
ALT 101 AST 71
Treatment Naive
Started Sof/Dac Jan 12, 2016
VL= <15 4 weeks in. AST/ALT normal.
VL=UNDETECTED 8 weeks in.
SVR4= Virus back. 3,300,000

Started generic Epclusa Sep. 23, 2017

4 weeks in <15 *Detected.
12 weeks in <15 *Not Detected.
16 weeks in <15 *Not Detected.
Finished 24 weeks treatment 3-17-18
SVR5 <15 Not Detected.
SVR 20 <15 Not Detected.
SVR 44 <15 Not Detected.

Thank you Jesus.
Thank you Dr. James
28 October 2016 at 1:34 am #24034
splitdog
- Topics: 5
- Replies: 374
- Total: 379
- Guardian Angel
@splitdog
October 20, 2016

http://www.gilead.com/news/press-releases/2016/10/gilead-announces-svr12-rates-from-four-phase-3-studies-of-a-oncedaily-fixeddose-combination-of-sofosbuvir-velpatasvir-and-voxilaprevir-in-treatmentna%C3%AFve-and-treatmentexperienced-genotype-16-chronic-hcvinfected-patients

splitdog@roadrunner.com

Genotype 3
VL 4,100,000
ALT 101 AST 71
Treatment Naive
Started Sof/Dac Jan 12, 2016
VL= <15 4 weeks in. AST/ALT normal.
VL=UNDETECTED 8 weeks in.
SVR4= Virus back. 3,300,000

Started generic Epclusa Sep. 23, 2017

4 weeks in <15 *Detected.
12 weeks in <15 *Not Detected.
16 weeks in <15 *Not Detected.
Finished 24 weeks treatment 3-17-18
SVR5 <15 Not Detected.
SVR 20 <15 Not Detected.
SVR 44 <15 Not Detected.

Thank you Jesus.
Thank you Dr. James
28 October 2016 at 3:11 pm #24040
thirdtimelucky
- Topics: 0
- Replies: 6
- Total: 6
- Novice
@thirdtimelucky
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
28 October 2016 at 3:56 pm #24043
Gaj
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- Guardian Angel
@gaj
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 https://fixhepc.com/forum/relapse-corner/1263-voxilaprevir-a-new-protease-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.

G3a since ’78 – Dx ’12 – F4 (2xHCC)
24wk Tx – PEG/Riba/Dac 2013 relapsed
24wk Tx – Generic Sof/Dac/Riba 2015/16 relapsed
16wk Tx – 12/01/17 -> 03/05/17 NS3/NS5a + Generic Sof
SVR7 – 22/06/17 UND
SRV12 – 27/07/17 UND
SVR24 – 26/10/17 UND
29 October 2016 at 4:26 am #24050
Dr James
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- Guardian Angel
@fixhepc
Vox is not available as a generic yet, but your SVR rate with either Sofosbuvir + Daclatasvir or Sofosbuvir + Velpatasvir will be >95%

YMMV
30 October 2016 at 2:42 pm #24069
vitrus
- Topics: 1
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- Total: 36
- Treatment Warrior
@vitrus
Yes, you may not need voxilaprevir. Sofosbuvir (an ns5b inhibitor) creates temporary resistance s282t that gets cleared by itself in 6-12 months. http://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.
http://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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961994/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786064/
http://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).

Gen 1b
VL pre treatment 29000 ME/ml
AST 32 ALT 94, F0
Started treatment 13 January 2017
Generic sofosbuvir/velpatasvir (Incepta)
VL 9 days into treatment <300 (undetected)
AST 13.8 ALT 22
Side effects: mild dehydration, not a problem at all if I drink water at night, nothing to worry about
Diet and gastric ph are very important with velpatasvir. One must think what and when to eat to keep gastric pH low. Side effects disappeared 2 weeks after, unless I ate anything < 4hrs before the pill. SVR60.
31 October 2016 at 2:52 pm #24080
vitrus
- Topics: 1
- Replies: 35
- Total: 36
- Treatment Warrior
@vitrus
Gilead announces SVR12 Rates From Four Phase 3 Studies of sofosbuvir + velpatasvir + voxilaprevir! (20 October 2016)
Filing FDA application very soon.
http://www.gilead.com/news/press-releases/2016/10/gilead-announces-svr12-rates-from-four-phase-3-studies-of-a-oncedaily-fixeddose-combination-of-sofosbuvir-velpatasvir-and-voxilaprevir-in-treatmentna%C3%AFve-and-treatmentexperienced-genotype-16-chronic-hcvinfected-patients
http://www.empr.com/idweek-2016–adult-infectious-diseases/high-efficacy-with-sofosbuvirvelpatasvir-voxilaprevir-for-pangenotypic-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.
http://www.pr-medicalevents.com/congress/aasld-2016/

Gen 1b
VL pre treatment 29000 ME/ml
AST 32 ALT 94, F0
Started treatment 13 January 2017
Generic sofosbuvir/velpatasvir (Incepta)
VL 9 days into treatment <300 (undetected)
AST 13.8 ALT 22
Side effects: mild dehydration, not a problem at all if I drink water at night, nothing to worry about
Diet and gastric ph are very important with velpatasvir. One must think what and when to eat to keep gastric pH low. Side effects disappeared 2 weeks after, unless I ate anything < 4hrs before the pill. SVR60.
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