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Post Info TOPIC: SOF/VEL and SOF/VEL/VOX
Tig


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RE: GT 3's and SOF/VEL trials
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Hi Canuck,

Thanks for the updates, I enjoy them. Much goes over my head, but everything I do, is very interesting. I like the information coming out of Barcelona this year. They appear to be learning a lot more about these new treatments, the RAV situation and how they impact success and potential failure rates. Seems like they are staying on top of things this year and are making strides in the right direction. More so than in recent years. The differences in the NS 3/4 PI's and the NS5A/B inhibitors and their combinations, are proving to be quite the topic for discussion. So much to learn though, but it appears they're trying! It's all very encouraging.



__________________

Tig

61 yo GT1A - 5 Mil - A2/F3 - (1996) Non Responder, (2013) Peg/Riba/Vic SOT:05/23/13 EOT:12/04/13 SVR 1-4 years!

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Another one, continuing the data dialog that has already been surfacing about treating GT3's (and all GT's) with velpa.

This one is was mostly in regard to GT1 numbers, but some generalities apply to 3's and other GT's.

Generated from highlights out of the "in progress" Barcelona Liver Meeting. C.

Triple therapy shows efficacy in treatment-experienced patients

BARCELONA A new three-pronged approach to hepatitis C virus effectively treated prior non-responders with genotype 1, according to a presenter at the International Liver Congress.

As increasing numbers of patients get treated, the number of patients that, cumulatively, will fail will increase over time despite rates of 95% or higher,Eric Lawitz, MD, of Texas Liver Institute, University of Texas Health Science Centre, San Antonio, said in a press conference. In our quest to get universal success for all patients, we need regimens that can take the next step to allow patients who have failed these really good regimens we have today and allow them to be successful. This is a small study but is groundwork for an evolving field.

Lawitz showed data from a small study with two fixed-dose treatment groups: Sovaldi (sofosbuvir)/velpatasvir/GS-9857 (Gilead Sciences; n = 24) and sofosbuvir/velpatasvir/GS-9857 plus ribavirin (n = 25).

Factors that may predict failure were evenly stratified across the two groups, Lawitz said, referring to age, BMI, ethnicity, genotype and previous treatment with direct-acting antivirals. Forty percent, he said, had previous NS5A experience.

Overall, the study showed an SVR rate of 98% with just one relapse in the ribavirin group and mostly mild to moderate adverse events.

The addition of ribavirin to three antivirals did not have any additional benefit, he said. The baseline resistance associated variants that would emerge as a result of treatment failure with antivirals did not reduce the rate of success. Having three antivirals with different mechanisms of action allow you to achieve 98% success rate irrespective of failure with other classes of antivirals. by Katrina Altersitz

Reference:

 

Lawitz, E. PS021. Presented at: International Liver Congress. April 13-17, 2016; Barcelona.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 62 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



Guru

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Thank you and contrats here as well on your ZERO



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



Guru

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Hi SF,

I cut and pasted the actual article now, below the link. smile C.

BTW - this article info is nothing earth shatteringly new - it's just a "recently written" article on the same info already "out there" - the data is still based on small numbers of subjects, and limited numbers of trials, especially pertaining to G3's - it is just presented and highlighted differently in this particular article.



-- Edited by Canuck on Thursday 14th of April 2016 06:46:59 PM

__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 62 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



Guru

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Hi Canuck,

It wants us to join the forum. It will not just display the article cry



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



Guru

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ARTICLE ABOUT SOF/VEL - in general, a synopsis of trials done, that included most GT's - of particular interest to me of course was one sentence, in regard to 1's and 3's:

 ... "The presence of pretreatment NS5A resistance-associated variants did not appear to affect SVR12 rates in most patients with genotype 1 or 3 HCV infection." ....

In regard to velpa (without riba), and velpa in general, this reiterates of some of it's "thought" valuable attributes, which may prove very meaningful, especially for the harder to treat G's, re-treatment of G's (or treatment of any G's packing DAA 5A RAV's). smile C.

http://www.medscape.com/viewarticle/854507 (below, if link doesn't open)

Title - "HCV:  Simpler 12-Week HCV Treatment on Horizon"

Data from two phase 2 clinical trials reveal that 400 mg sofosbuvir plus 100 mg velatasvir is a well-tolerated and highly effective treatment for patients infected with hepatitis C virus (HCV) genotypes 1 to 6. One study tested 12 weeks of therapy in treatment-experienced patients, whereas the other tested the same regimen in treatment-naive patients.

The two studies were published online November 10 in theAnnals of Internal Medicine. Both studies had a randomized, open-label design.

Previously Treated Genotypes 1 or 3 Respond

In one of the studies, Stephen Pianko, MD, PhD, from Monash Health in Clayton, Australia, and colleagues tested the combination in patients with HCV genotypes 1 or 3 who had failed a prior therapy. Patients with genotype 3 were excluded if they had failed a prior experimental or approved direct-acting antiviral HCV treatment, but similar restrictions were not made for patients with genotype 1 infection.

The researchers randomly assigned patients to treatment with sofosbuvir (400 mg) and either 25 or 100 mg velpatasvir, with or without ribavirin. Overall, the combination of sofosbuvir and velpatasvir appeared safe and effective in these pretreated patients.

Although the study was not powered for comparisons among treatment groups, the researchers did note that the sustained virologic response rates at 12 weeks (SVR12) in patients infected with HCV genotype 3 were numerically higher among those treated with 100 mg velpatasvir than in those treated with 25 mg velpatasvir.

Moreover, the SVR12 rates in the 100-mg treatment group compared favorably with those previously reported for other regimens, according to the authors. In contrast, patients with genotype 1 HCV infection appeared to have similar rates of SVR12, regardless of velpatasvir dose or the presence of absence of ribavirin.

The presence of pretreatment NS5A resistance-associated variants did not appear to affect SVR12 rates in most patients with genotype 1 or 3 HCV infection.

Treatment-Naive Patients With Genotypes 1 to 6 Respond

In a separate study, Gregory T. Everson, MD, from the University of Colorado, Denver, in Aurora, and colleagues enrolled previously untreated, noncirrhotic patients and demonstrated high rates of SVR12 across genotypes 1 to 6. In the case of patients infected with HCV genotypes 1 or 2, SVR rates were lower at 8 weeks of treatment when compared with 12 weeks of treatment.

The investigators documented low rates of serious adverse events and had only one patient discontinue as a result of serious adverse events.

"This is, to our knowledge, the first demonstration of a [direct-acting antiviral] combination with pangenotypic activity against HCV genotypes 1 to 6. The SVR rates in this study for treatment-naive noncirrhotic patients were similar to those observed with standard-of-care regimens," write Dr Everson and colleagues.

"It is important to have a simple regimen that works against all genotypes," said Naim Alkhouri, MD, a hepatologist at the Cleveland Clinic in Ohio in an interview with Medscape Medical News. He was not affiliated with the current study but has consulted for Gilead on other projects.

He said the results represent an advance for patients because such a treatment regimen would preclude the need for HCV genotyping before the initiation of treatment. Moreover, such treatments would represent a simple, all-oral, effective, and well-tolerated regimen.

Both trials were funded by Gilead Sciences. Dr Pianko reports receiving personal fees or other support from the following companies: Gilead Sciences, Roche Diagnostics, AbbVie, Bristol-Myers Squibb, and Merck. Several coauthors report one or more type of financial or nonfinancial support from one or more of the following companies: Gilead Sciences, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, Merck, Boehringer Ingelheim, Conatus, Galectin, Intercept, Lumena, ViiV, UpToDate, and ViralEd. One coauthor is an employee and stockholder of Gilead Sciences. Dr Everson reports grants and personal fees from Gilead Sciences, AbbVie, Merck, Bristol-Myers Squibb, and Janssen Pharmaceutica, and several patents for liver function diagnostics with exclusive licensing to HepQuant and royalty payments to the University of Colorado and himself. Several coauthors report personal fees, grants, or other support or relationships with one or more of the following companies: Gilead Sciences, Bristol-Myers Squibb, ViiV Healthcare, Vertex Pharmaceuticals, Pfizer, Merck, AbbVie, Janssen Pharmaceutica, Tacere Therapeutics, Salix Pharmaceuticals, Tobira Therapeutics, Intercept Pharmaceuticals, Galectin Therapeutics, Hologic, Genentech, Hoffmann-La Roche, MassBiologics, Enanta Pharmaceuticals, and Idenix Pharmaceuticals. Two coauthors report they are employees of and shareholders in Gilead Sciences. Dr Alkhouri is on the advisory board for Gilead Sciences.

Ann Intern Med. Published online November 10, 2015. Pianko full textEverson abstract

 



-- Edited by Canuck on Thursday 14th of April 2016 06:28:36 PM

__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 62 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



Guru

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Mallani,

Yes, regarding my 8 week SOF/VEL triple with the GS-9857 - this (NS3/4A protease inhibitor) GS-9857 has little information on it even if you search for it, other than general descriptions I have read. All I have been able to find out about this GS-9857, is that (similarly to the development of NS5A VEL) this particular protease inhib. is hoped to be of better design - "more pan", perhaps better more "potent", thereby more effective for me as a GT3a.

Synthesized from a couple different description/article sources I have read, this (NS3/4A protease inhib.) GS-9857 was typified thus:   ... "active for 1b and 3a's, an Aco-molar inhibitor, (thought more) panogenic (but perhaps) less potent in GT3" ... 

Too bad for me, that I cannot know more about this GS-9857 drug I am taking, other than the minor surmizing of what some of its mild sides might be, and, that its added use for a triple therapy is in keeping with the thought-best-at-the-moment multipronged attack theory (throwing the kitchen sink at it/shotgun approach). When in doubt, more is better?

On the NS5A front (replication complex inhibs.) - in the recent popular aversion to taking effective RBV, in the quest for one size fits all pan treatments, and shorter treatment periods, the upward onslaught in development of NS5A's (from from DAC, Ombi, Ledi, Elba) VEL does seem to be weighing in heavily on the side of "pan" enough, "potent" enough for GT3's, and, potent enough for shorter treatments. But, as you pointed out previously in your tutorials on "cross-over" (widely overlapping RAV's) seen between all these NS5A's (and perhaps especially problematic stil,l are high viral loaders and GT3 people) so that even with the likes of VEL and Elba, the wrinkles are still not fully ironed out - thus why we keep seeing this falling back to upping a double therapy to a triple by throwing in the kitchen sink? I think we ARE maybe getting closer to ironing everything out.

What remains for me is the fear of not being able to completely minimize failures for all GTs with pans, and failures with fit persisting RAV's to the newest NS5A's and NS3/4A's. Perhaps one saving grace WILL be the higher resistance factor of the GS-9857, and the higher pan potency with both VEL and GS-9857.

In my limited reading and understanding, I believe the vel combo's are my best bet as a 3a. Robertamx will hopefully get accepted into the most recent sov/vel/GS-9857 trial, and to tell you the truth, I would have rather been in the triple arm of his trial 12 weeks sof/vel with GS-9857, rather than in my triple trial of 8 weeks sof/vel GS-9857, simply because my uneducated guess is that more is better. C.

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 62 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



Guru

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Hi Canuck,

You should do well. It's about time Gilead followed AbbVie and adopted the shotgun approach.

Unlike V-Pak, all of the Gilead drugs are top class, and having a nucleoside NS-5B inhibitor puts this combo way ahead of AbbVie.

GS-9857 appears to be a potent NS-3 blocker with a higher resistance profile compared with the previous antiproteases.

The duration of treatment is the unknown for this combo. The Phase 2 Trials showed 6 weeks was not enough. I hope 8 weeks does the job for you. There was a suggestion that the Trials should include 10 and 12 week arms.

Interesting that the IL28B gene has resurfaced. It was thought this was only important for Interferon regimes. To find the CC's do better with the new DAA's raises a lot of questions.

Keep us posted. This may be the ideal combo for Geno3. Cheers.



__________________

Geno 1b, IL28B CT,  x3 prior relapser,  ex-cirrhotic, 74 yo, did 48 weeks with Victrelis/Peg./Riba.  VL 1.28m at start, UNDET. at 8 ,12 ,16 ,24 ,30  and 48 weeks.  EOT 15 Feb 2013 , UNDET. at EOT + 28 weeks. SVR!  Still Undet. at EOT +4 years

Malcolm



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Big Smile,

Great news Canuck. I am happy and you waited long enough for it. Please keep us posted and I know you will have a good weekend now

 

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



Guru

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SOF/VEL and SOF/VEL/VOX
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As I am a GT3a, I have been doing much reading (in many areas) about many aspects pertaining to the difficult of having and treating GT3's.
GT3a "distinctions/idiosyncrasies" if you will. As some better drug treatments are now coming along for us 3's, who may have felt something like a minority orphan up until now, perhaps we will now start to see much better feedback on how newer efforts in treatment are working for us, via trial data, etc.
 
I have just started a SOF/VEL/GS-9857 8 week trial (lucky, lucky, lucky). Had my Hep c been discovered earlier ... say ... like anytime in the last 40 plus years!, most of you can well imagine what drugs would have been available to me, even up to a few short years ago. It does indeed look like restrictive limitations may now be starting to decline for 3's.
 
During my most recent appointment with my hep doc, on my "day one" of starting the already-decided-on triple sof/vel/GS-9857 treatment, we spoke ever so briefly (again) about drugs for 3's, period, and treatment options for GT3 failures.  We again skimmed over other trials I had previously asked him about  - ABT 493/530 (NS 3/4A + 5A),  Grazo/Elba (NS 3/4A + 5A) to which many variations of added 5B or differing 5A (and /or RBV) are being trialed. He also mentioned a newer ABT regime to come?, and, another "molecule" one ? (I forget now - but I will ask him again what exact trials he may be referring to, and share it).
 
You may be interested to know - for my trial, WHO really made the final decision as to which arm I got (sof/vel alone for 12 weeks, or my 8 week triple arm??) after the humans were finished collecting and digesting the info on me - the decision was made by a computer!
 
Mallani has posted much good info regarding 5A and 5B choices suited to particular GT's. Genetic predisposition/ RAV's taking the driver's seat, something as simple as IL28 determination prior to treatment being a useful too, was one of only many very worthy topic's he has brought up.
 
 
I happened to recently find out I am a IL28 CC (not a CT or TT), which is somewhat comforting to know, prior to starting a treatment.
 
It is also comforting to know that Gilead, in my trial and all trials they do, and others pharmas, will keep amassing and researching much genetic determination data for current and future study, which should prove of benefit to me and others (even if my genetic testing info is not immediately forthcoming or known to me, or others now).
C. 


__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 62 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)

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