Telaprevir 208 study; 2X daily 80% SVR!!!

Question

Fresh off the presses at AASLD!!!!- Willy
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More than 80% of Hepatitis C Patients Treated in Study C208 Achieved an SVR with Telaprevir-Based Regimens

    * 83% SVR achieved with twice-daily regimen of telaprevir dosed with PEGASYS and ribavirin
    * Results highlight the use of response-guided therapy in managing treatment outcomes
    * Similar safety and tolerability observed between telaprevir-based regimens dosed either twice daily or three times daily


BOSTON, Oct 31, 2009 (BUSINESS WIRE) -- More than 80 percent of hepatitis C patients in each arm of the Phase 2 Study C208 achieved a sustained viral response (SVR) with a telaprevir-based regimen according to results of an intent-to-treat (ITT) analysis announced today by Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX). The data from Study C208 will be presented in an oral presidential plenary session at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which began yesterday in Boston. Telaprevir is a hepatitis C virus (HCV) protease inhibitor being developed by Vertex Pharmaceuticals Incorporated in collaboration with Tibotec and Mitsubishi Tanabe Pharma.

Study C208 explored telaprevir-based regimens dosed either every 12 hours (q12h; twice daily) or every eight hours (q8h; three times daily) combined with either peg-IFN-alfa-2a (PEGASYS(R)) or peg-IFN-alfa-2b (PEGINTRON(R)) and ribavirin (RBV), for 12 weeks followed by an additional 12 weeks of peg-IFN and RBV in a response-guided trial design that included 161 treatment-naïve patients (intent-to-treat analysis) with genotype 1 hepatitis C virus (HCV) infection. Across the four arms, SVR rates were 82 and 83 percent in patients treated with the every 12 hour telaprevir-based regimen (PEGINTRON and PEGASYS, respectively) and 81 and 85 percent in patients treated with the every 8 hour regimen (PEGINTRON and PEGASYS, respectively). For the majority of patients, these SVR rates were obtained with a 24-week telaprevir-based regimen.

"With high SVR rates and similar safety outcomes between the twice-daily and three-times-daily treatment groups, the results from this exploratory study support the future evaluation of telaprevir-based regimens dosed twice daily," said Professor Patrick Marcellin, M.D., from Beaujon Hospital in Clichy, France. "These results also highlight the potential future role for response-guided therapy with the goal of improving treatment outcomes and potentially shortening the duration of therapy for the majority of patients."

Study C208 Results                                         RVR*                                              SVR**
   
TVR (q12h/peg-IFN alfa-2a/RBV) (n=40)                 83% (n=33)                                 83% (n=33)
   
TVR (q12h/peg-IFN alfa-2b/RBV) (n=39)              67% (n=26)                                 82% (n=32)
   
TVR (q8h/peg-IFN alfa-2a/RBV) (n=40)                 80% (n=32)                                 85% (n=34)
   
TVR (q8h/peg-IFN alfa-2b/RBV) (n=42)                 69% (n=29)                                   81% (n=34)
   

* Rapid Viral Response: Undetectable HCV RNA at week 4

** Sustained Viral Response: Undetectable HCV RNA 24 weeks after the end of treatment

alfa-2a: ===PEGASYS

alfa-2b: === PEGINTRON

banarep · Answer

I think Study 107looked at prior treatment failures and Realize looks at over 600 prior treatment failures on treatment for 48 weeks, with either a lead in or starting meds right away.

Willy50 · Answer

Study C208 explored telaprevir-based regimens dosed either every 12 hours (q12h; twice daily) or every eight hours (q8h; three times daily) combined with either peg-IFN-alfa-2a (PEGASYS(R)) or peg-IFN-alfa-2b (PEGINTRON(R)) and ribavirin (RBV), for 12 weeks followed by an additional 12 weeks of peg-IFN and RBV in a response-guided trial design that included 161 treatment-naïve patients (intent-to-treat analysis) with genotype 1 hepatitis C virus (HCV) infection.

banarep · Answer

I think so.  the Realize trial is the one with relapsers, etc in it.

neptune235 · Answer

this was done with treatment-naive patients, right?

Rockerforlife · Answer

Soon there will be "CURE"...if they keep going at this rate.

newleaf09 · Answer

Very interesting.  It was a small study, like most phase 2's are, but there was a difference in RVR rates between the 2 interferon forms, alpha-2a and alpha-2b, which did not make so much difference in the end game.  Thanks for posting, Willy

WriteItDown · Answer

Tibotec's protease inhibitor TMC435, currently in Phase IIb trials, also has a once-a-day dosing regimen.

Willy50 · Answer

Interesting perspective if one compares it to Boceprevir;

http://www.thestreet.com/story/10619851/1/vertex-hep-c-drug-cures-80-at-new-dose-study.html

We will soon see other protease and polymerase inhibitors that will be competetive or better than this; some are being tested for dosing once per day (such as the new Shering 2nd generation PI which follows Boceprevir.

Vertex also has a few new TVR second and 3rd generation drugs in development.
They are currently testing their new polymerase inhibitor VX-222 in trials right now.  They expect that this is the compound which they will combine with TVR, perhaps yet this year for a short phase 1 trial.

best,
Willy

Willy50 · Answer

It is true that you cannot easily get into a trial right now, but TVR should be available in about 1-1.5 years.  Vertex says that they will apply for a NDA mid 2010.

Once it is approved you should also have some more information to base evaluation of retreating with a PI.  I'm not sure that anyone can tell you that you can't clear and SVR once RBV is added.

Vertex is also starting...perhaps this year their Stat C combination of  polymerase and protease inhibitors.  Josh Boger, then CEO of Vertex said that he expected that combo to be approved in 2014or 2015....give or take.  IF TVR can deliver 80-85% in a trial, there may even be a bit more room for improvement.  In adding a complementary PI it very well may be that the amounts of IFN or RBV could be reduced or even eliminated.

We may soon have many faster and more effective forms of treatments.  I believe that one will cure you. 

This is just the beginning.

best,
Willy

DoubleDose · Answer

This really is pretty incredible stuff!  24 weeks, in Genotype 1's, and an 83% cure rate......things are moving in the right direction.  I would expect that in ten years, with multiple cocktail approaches and immune booster type drugs that we should be approaching the 90% plus cure rate....maybe even getting close to 100% eventually. 

 The best aspect of this is the shorter treatment times, which should translate into much less long term damage, and a much easier treatment course.  If people feel less intimidated by treatment, and  fully expect to be cured, then just about everyone will treat. 

 I do believe that we will continue to see the combined use and inclusion of pegylated interferons, and Ribavirin with the new cocktail therapies for a long time, if not permanently.  From what my doctors told me when I treated, the inhibitor drugs can drop the load dramatically, but cannot eradicate the virus on their own.  Still, 24 weeks of all the above mentioned drugs is really a cakewalk, compared to what many of us had to endure!  Great news for future treaters indeed.

DoubleDose