EASL 2009 Telaprevir G-4 Results

[Willy50]

http://www.kenes.com/easl2009/Orals/153.htm

Session Title: Parallel Session 1: HEPATITIS C VIRUS DRUG DEVELOPMENT I
Presentation Date: Apr 23, 2009

RESULTS OF A PROOF OF CONCEPT STUDY (C210) OF TELAPREVIR MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAÏVE GENOTYPE 4 HCV PATIENTS

Y. Benhamou1, J. Moussalli1, V. Ratziu2, P. Lebray1, V. Gysen3, K. de Backer3, A. Ghys3, R. van Heeswijk3, T. Vangeneugden3, G. Picchio4, M. Beumont-Mauviel3
1Hôpital Pitié-Salpêtrière, 2Université Pierre et Marie Curie, Paris VI, Paris, France, 3Tibotec BVBA, Mechelen, Belgium, 4Tibotec Inc., Yardley, PA, USA

Background: C210 is an ongoing, partially blinded, randomized, Phase 2a study of telaprevir (TVR), administered as monotherapy and in combination with peginterferon alfa 2a (Peg-IFN) and ribavirin (RBV), investigating early viral kinetics of HCV-RNA decay in treatment-naïve subjects with genotype 4 infection. We report results of the primary analysis conducted at day 15 of treatment.


Methods: HCV genotype 4 subjects were randomized to receive

TVR 750mg q8h alone (arm A; n=8),

TVR with Peg-IFN 180µg/week and RBV 1000-1200mg/day (arm B; n=8),

or Peg-IFN and RBV plus placebo (arm C; n=8) for 15 days.

Viral load was measured using Taqman assay (limit of detection 1-log increase in HCV-RNA above nadir or >100 IU/mL HCV-RNA after previously undetectable HCV-RNA. An ITT analysis was performed when all treated subjects had completed 15 days of dosing or had discontinued earlier.


Results: 38% of enrolled patients were Egyptian and 25% were Caucasian; none had cirrhosis and 58% had HCV-RNA >800,000 IU/mL. Genotype 4a was the most prevalent subtype (50%).

The mean (SE) log10 changes in HCV-RNA at days 3/15 were -1.2(0.28)/-0.9(0.46), -2.1(0.29)/-3.4(0.65), and -1.0(0.26)/-2.0(0.40), while the mean (SE) log10 maximum HCV-RNA change was -1.4(0.30), -3.5(0.48) and -2.0(0.40) for arms A, B and C, respectively.

By day 15, 0%, 13%, and 0% of subjects had undetectable (< 10 IU/mL) HCV-RNA in arms A, B and C, respectively; vBT during the dosing period was observed in 5, 1 and 0 patients, respectively. The overall incidence of adverse events (AEs) was similar across arms and in line with previous reports. One patient in arm A had a serious AE that was considered unrelated to TVR but led to treatment discontinuation.


Conclusions: TVR in combination with Peg-IFN and RBV had greater activity against HCV genotype 4 than Peg-IFN and RBV alone or TVR monotherapy. The potential role of TVR in combination with Peg-IFN and RBV in the treatment of HCV genotype 4-infected patients remains under investigation.

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(I think I'll try to decipher the above results-Willy)

Arm A            Day 3   -1.2 log        Day 15  -0.9 log drop     % UND-  0%       Max log delta  -1.4
(TVR monotherapy)

Arm b            Day 3     -2.1            Day 15   -3.4                  % Und-  13%      Max log delta  -3.5
(TVR TID plus SOC)

Arm c            Day 3     -1.0             Day 15  -2.0                    % UND-  0%       Max log delta  -2.0
(tvr PLACEBO plus SOC)

Jim or anyone; at some point we will see this on a nice graph or chart but in the meanwhile this is how I decipher the results.  I believe that the genotype 2 and 3 results may follow this pattern but of course it is even more jumbled since there are 2 different genotypes.  Better charts will follow I'm sure.  (by the way delta = change)

Willy

[mikesimon]

I always assume people want to know about aspects of HCV even if they don't apply directly to them.
Anyway, these results look very encouraging. I especially liked the cirrhosis numbers. So many people are told that they cannot treat because they're cirrhotic. This seems to hold out some hope for them. I wish it had been available back before I went to surgery.
I really hope this drug gets to the public soon. It seems like we've been waiting forever.
Be well,
Mike

[Willy50]

Mike, Maybe I should have posted Genotype 4 instead of G-4, or have lead with it.  I abbreviated since I thought that too long of a title wouldn't be seen.

Anyway..... looks like this is Prove 3 data and was probably intended for another thread.

LOL; I'm thrilled that someone was interested enough to post, however.  ; )  
(not that many geno 4's in the USA.)

Best,
Willy

[mikesimon]

Telaprevir Data Presented at EASL

"....... [1] Non-responders are defined as patients who never achieved undetectable HCV RNA during or at the end of prior therapy.

[2] Relapsers are defined as patients who achieved undetectable HCV RNA at the completion of prior treatment, but relapsed during follow-up.

[3] Breakthroughs are defined as patients who had undetectable HCV RNA during prior treatment, but had detectable HCV RNA before the end of prior treatment.

Sixty-nine and 76% of prior relapsers in the 24- and 48-week telaprevir-based treatment arms, respectively, achieved SVR as compared to 20% in the control arm, and 39% and 38% of prior non-responders in the 24- and 48-week telaprevir-based treatment arms, respectively, achieved SVR as compared to 9% in the control arm. A sub-analysis showed that 53% and 45%, respectively, of patients with cirrhosis in the 24- and 48-week telaprevir-based treatment arms achieved SVR compared to 8% in the control arm – these results were similar to those obtained for patients without cirrhosis.

In PROVE 3, an overall relapse rate of 13% (10 of 76 patients) was observed in patients in the 48-week telaprevir-based treatment regimen arm, while patients in the control arm relapsed at a rate of 53% (18 of 34 patients). A third arm of the study, evaluating a 24-week telaprevir-based regimen, showed a similar SVR rate compared to the 48-week telaprevir arm and an overall relapse rate of 30% (26 of 87 patients). In a completers’ analysis, a relapse rate of 4% (2 of 53 patients) was observed in patients who completed treatment with a 48-week telaprevir-based treatment regimen, while patients who completed treatment in the control arm relapsed at a rate of 52% (17 of 33 patients). A third arm of the study, evaluating a 24-week telaprevir-based regimen, had a relapse rate of 28% (22 of 80 patients) in patients who completed treatment with a 24-week telaprevir-based regimen. These results suggest that a telaprevir-based regimen that includes a total of 48 weeks of treatment with peg-IFN and RBV including 12 weeks of telaprevir may be warranted in treatment-failure patients. REALIZE, a Phase 3 study designed to evaluate this treatment regimen in non-responders (null and partial responders) and relapsers, is currently underway......"

[Willy50]

trying to re-adjust the table-willy

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I think I'll try to deciper these results;

Arm A       Day 3   -1.2 log     Day 15  -0.9     % UND-  0%      Max log delta  -1.4
(TVR monotherapy)

Arm b        Day 3     -2.1        Day 15   -3.4    % Und-  13%     Max log delta  -3.5
(TVR TID plus SOC)

Arm c        Day 3     -1.0         Day 15  -2.0     % UND-  0%     Max log delta  -2.0
(tvr PLACEBO plus SOC)