Telaprevir at EASL

[Willy50]

I don't think I've seen this yet here....

http://www.vrtx.com/easl2011.html

2 late breaker presentations;

#1363: "VX-222 with TVR Alone or in Combination with Peginterferon ALFA-2A and Ribavirin in Treatment-Naïve Patients With Chronic Hepatitis C: ZENITH Study Interim Results"

#1369: "Teleprevir Substantially Improved SVR Rates Across All IL28B Genotypes in ADVANCE Trial"
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4 oral presentations

"REALIZE Trial Final Results: Telaprevir-Based Regimen in Genotype 1 Hepatitis C Virus Infection in Patients with Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin"


"Subanalyses of the Telaprevir Lead-in Arm in the REALIZE Study: Response at Week 4 is Not a Substitute for Prior Null Response Categorization"


"Evolution of Treatment-Emergent Resistant Variants in Telaprevir Phase 3 Clinical Trials (ADVANCE, ILLUMINATE, REALIZE)"


"Similar SVR Rates in IL28B CC, CT or TT Prior Relapsers, Partial- or Null-Responders Patients Treated with Telaprevir/Peginterferon/Ribavirin: Retrospective Analysis of the REALIZE Study"
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There are a total of 15 Vertex presentations during EASL

[Willy50]

It appears we may see more data than I thought on the quad therapy trial; note the second "highlight" ("The first data from an ongoing Phase 2 study evaluating 12- and 24-week response-guided regimens").  With some luck we may see in immediate viral kinetics of the first days and weeks of the trial, not just a the 4 week outcomes.  The 24 week outcomes will also be of interest, but to my knowledge these will be for people who did not meet the 4 and 12 week goals; we will see.  willy
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http://finance.yahoo.com/news/New-Data-on-Telaprevir-and-bw-203373230.html?x=0&.v=1

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX - News) announced today that 15 abstracts on the company’s medicines in development for hepatitis C, including its protease inhibitor, telaprevir, and polymerase inhibitor, VX-222, were accepted for presentation at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany, March 30 to April 3, 2011.

Highlights of data presentations include:

    Complete results from the pivotal Phase 3 REALIZE study will be presented for the first time. Topline results from this study, which evaluated telaprevir in combination with pegylated-interferon and ribavirin in people who had not achieved a viral cure (SVR) with currently available medicines, were announced in September 2010.

    The first data from an ongoing Phase 2 study evaluating 12- and 24-week response-guided regimens of telaprevir and VX-222 in combination with pegylated-interferon and ribavirin will be presented during a late-breaker session (Abstract #1363).

    Retrospective analyses of the relationship between IL28B genotype status and rates of viral cure with telaprevir-based combination therapy from the pivotal Phase 3 studies of REALIZE and ADVANCE will also be presented.

[Willy50]

Steve, the way that Vertex has handled this in the past is that they will not give finaal results until after all of the results are in.  Seeing as how they just started a new arm, a 5th arm that will be another 12 weeks plus 24 weeks EOT.  That means that the actual total trialinfo may be released in a year.  More likely, they often will reveal the preliminary results; lets say EOT or the data from SVR12.

It is also quite possible that a phase 2B trial will start before then or about then.  The best response, the best chances for the drug combo will probably be seen in the new trial design.

Sometimes you can divine answers by gleaning info from posts on boards like this.

Willy

[SteveOC]

Been wondering when that data would be released, I think now I can find out what dose of 222 I was given which I am very interested in knowing. Still awhile before my safety follow up but I did get called in Tuesday for a draw to confirm the relapse but only saw the phlebotomist and the study nurse so no answers to my zillion and a half questions yet.

[Willy50]

smidge of info on quad (VX-222 &Telaprevir with  SOC) therapy;

http://www1.easl.eu/easl2011/program/Posters/Abstract3.htm
(visit the link for the complete story w/ table)

VX-222 WITH TVR ALONE OR IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAïVE PATIENTS WITH CHRONIC HEPATITIS C: ZENITH STUDY INTERIM RESULTS

A.M. Di Bisceglie1*, D.R. Nelson2, E. Gane3, K. Alves4, M.J. Koziel4, C. De Souza4, T.L. Kieffer4, S. George4, R.S. Kauffman4, I.M. Jacobson5, M.S. Sulkowski6, ZENITH Study Team
1St Louis University School of Medicine, St. Louis, MO, 2University of Florida College of Medicine, Gainesville, FL, USA, 3Auckland City Hospital, Auckland, New Zealand, 4Vertex Pharmaceuticals Incorporated, Cambridge, MA, 5Weill Cornell Medical College, New York, NY, 6Johns Hopkins University, Baltimore, MD, USA. ****@****

Background and aims: ZENITH is assessing the safety, tolerability and antiviral activity of VX-222 with TVR, an HCV polymerase and protease inhibitor, respectively alone (DUAL) or with peginterferon alfa-2a (PEG) and ribavirin (RBV) (QUAD) in chronic HCV genotype 1 treatment-naïve patients.
Methods: 106 patients were randomized to 1 of 4 arms: A (n=18): VX-222 100mg, TVR 1125mg bid; B (n=29): VX-222 400mg, TVR 1125mg bid; C (n=29): VX-222 100mg, TVR 1125mg bid, PEG 180µg/week, RBV 1000-1200mg/day; and D (n=30): VX-222 400mg, TVR 1125mg bid with the same doses of PEG and RBV, for 12 weeks. Additional 12 or 24 weeks of PEG/RBV treatment is dependent on viral responses at week 2 and 8. Results are presented for all patients who had 4 weeks treatment.

Results: Both DUAL arms were terminated after patients experienced on-treatment viral breakthrough (vBT). No vBT has been observed in either QUAD arm. Median time to undetectable HCV RNA was 4 and 2 weeks in Arms C and D, respectively. The majority of patients in arm D had undetectable HCV RNA by week 2; RVR rates were high in both QUAD arms (Table). Most adverse events (AEs) were mild or moderate; with diarrhea (37%, n=39), fatigue (36%, n=38), nausea (34%, n=36) and rash (23%, n=24) most frequently observed. One patient (arm B) discontinued due to acute renal failure at week 2. No patient discontinued due to gastrointestinal events.

Summary and Conclusions: Both DUAL telaprevir/VX-222 arms were stopped due to on-treatment vBT. Conversely, in this interim analysis, no patients in either QUAD arm experienced vBTs. Median time to undetectable HCV RNA in arm D was 2 weeks and the majority (86-87%) of patients had undetectable HCV RNA at week 4. Patients are being followed for SVR and safety.

[Willy50]

You may not know what this is about but the very first presentation that I listed is very similar to the other acclaimed DAA trial that got a lot of hoopla today; the Pharmasset twin oral agents;PSI-938 and PSI-7977.

The Vertex presentation will be about Telaprevir and VX-222.  These may be very similar outcomes, viral kinetics, but who knows?

It will be interesting to see how these two drug trials compare.

For what it is worth..... the 2 arms in this trial done with no IFN or RBV were discontinued; breakthroughs occurred.

The Vertex trials will likely focus on response instead of "cure" SVR rate and the results will be preliminary, particularly since a 5th arm has opened up with the same oral DDA combined with RBV.

willy