Medivir Announces Final Results from TMC435 Phase IIb ASPIRE (C206) Study

[spectda]

STOCKHOLM, November 2, 2011 /PRNewswire/ --

TMC435-Based Therapy Significantly Improved Viral Cure Rates in Patients Who Failed Prior Treatment for Hepatitis C
- ASPIRE: All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared with control group (pegylated interferon and ribavirin alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders -
- Once daily TMC435 was generally safe and well tolerated at all doses and treatment durations -
Medivir AB (OMX: MVIR), a research-based speciality pharmaceutical company focused on infectious diseases, today announces final results from the ASPIRE study. This phase IIb study evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with genotype-1 chronic hepatitis C whose prior treatment with PegIFN and RBV was unsuccessful either because they relapsed, had a partial response or had a null response.
Data from the ASPIRE study showed that patients in each of these subgroups who were treated with TMC435-based combination therapy achieved superior rates of sustained virologic response (viral cure) compared with those retreated with PegIFN and RBV alone.
Charlotte Edenius, Executive VP Research and Development, of Medivir commented, "We are extremely pleased with the final results from the ASPIRE study showing high viral cure rates and a favourable safety and tolerability profile in these difficult to treat genotype-1 hepatitis C patients whose prior treatment was unsuccessful. These results may provide new optimism for people who have failed on previous therapy, including those with advanced liver disease. We are highly committed to the broad and rapid development of TMC435 and global pivotal phase III clinical trials are currently well underway."
ASPIRE (C206) - Design
TMC435, a potent, once-daily, oral hepatitis C virus protease inhibitor, is being developed by Tibotec jointly with Medivir. The randomized, placebo-controlled, double-blind ASPIRE study evaluates the effect of TMC435 in combination with pegylated-interferon and ribavirin in 462 patients infected with genotype-1 hepatitis C virus who have failed prior treatment with PegIFN/RBV. The primary endpoint was proportion of patients with undetectable HCV RNA 24 weeks after the planned end of treatment (SVR24).
The study includes patients who have relapsed, achieved partial response, or achieved no response (null responders) to PegIFN/RBV treatment. 62 percent (287/462) of patients had advanced liver disease, periportal or septal fibrosis or cirrhosis (scarring of the liver) upon study entry (Metavir score F2-F4).
Patients were equally randomized to one of seven different treatment arms, six TMC435 treatment arms and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with 48 weeks of PegIFN/RBV. The results are based on the intent-to-treat (ITT), population which included all randomized patients who took at least one dose of the study medication.
Results - Efficacy  
In this final analysis, all subgroups of treatment-experienced patients who failed previous PegIFN and RBV treatment, achieved substantially higher virologic response rates following treatment with TMC435-containing regimen at all doses and durations, compared with PegIFN and RBV alone.
Regardless of treatment duration all TMC435 treatment arms showed significantly improved effect on SVR24 versus PegIFN/RBV alone.

[nygirl7]

"you guys are lucky, when I went through Tx, blah, blah, blah"  :o)


Big Daddy there are a whole bunch of us on here who can say that already ;)

[Jefferyz]

This TMC 435 stuff works pretty good. While taking it for the 12 weeks I had none of the side that come with the other 2 just realeased. dont get me wrong I had some bad rough sides from the riba and interfer but not much fr om the TMC435. Ive just been approved to stop all Meds on Wed.the 16th  The end of my 24 weeks on phase lll trial.  Went to my primary Doc on the side 3 and a half weeks after starting the meds and got a undetectable result. and must still be or they would continue me on riba/inter for another 6 months. Boy cant wait only another 3 days of riba/ inter to go.

[BigDaddy_59]

Great numbers for partial and null responders especially and low Sx's comparable with PegRiba.
Another arrow for our quiver!!!
Soon we WILL  have that 100% cure and us "oldtimers" will be saying, "you guys are lucky, when I went through Tx, blah, blah, blah"  :o)
Thanks for the heads up spectda or whatever your name really is...

[spectda]

At first glance seems to be a better choice then Incivek or Victrelis and very likely to be approved next.
Good luck

[printze]

Very interesting lets see what the final repports say when trisls end .Future looks very promising for us. I t willbe done ,soon we will have a short treatment, minimal side effects, 100% cure rate across the board . Fingers crossed . KEEPING HOPEFUL.  

[spectda]

forgot the link:
http://www.prnewswire.com/news-releases/medivir-announces-final-results-from-tmc435-phase-iib-aspire-c206-study-133065613.html

"About TMC435
TMC435 is a highly potent and selective once-daily (q.d.) investigational drug that is being jointly developed by Tibotec Pharmaceuticals and Medivir to treat chronic hepatitis C virus infections.
TMC435 has received "Fast Track" designation by the U.S. Food and Drug Administration ("FDA") for the treatment of chronic hepatitis C (CHC) genotype-1 infection. This is based on TMC435's potential to address unmet medical needs in the treatment of chronic HCV infection. TMC435 is currently being developed in three global phase III studies, QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment. In parallel with these trials, phase III studies for TMC435 in Japan, in both treatment naive and treatment experienced hepatitis C genotype-1 infected patients, are ongoing."

"Results - Safety and Tolerability
TMC435 was generally safe and well tolerated and overall incidence of adverse events (AEs) was similar across treatment groups. Most of the AEs were grade 1 or 2 in severity. Serious AEs (SAEs) were reported in 6.1% subjects in the placebo and in 7.8% of the patients treated with TMC435. AEs leading to treatment discontinuation were reported in 4.5% of the placebo patients and in 7.8% of the TMC435 treated patients. Patients in the TMC435 ASPIRE treatment groups had overall longer treatment duration than patients in the placebo group due to a higher frequency of early discontinuation in the placebo group due to treatment failures (i.e. reaching viral stopping rules). The most common AEs during the treatment period were headache, fatigue, pruritus and influenza-like illness. Incidence was similar across treatment groups and the level of AEs and frequency were consistent with the prior phase IIb (PILLAR) study in treatment-naïve hepatitis C patients of TMC435.
In the safety analyses, special attention was given to the following AEs of interest: hepatobiliary AEs, pruritus, rash and anemia. Most AEs of interest were grade 1 or 2 in severity and infrequently led to treatment discontinuation. For each category of AEs of interest the incidence was similar for the TMC435 treatment arms and control arm.
Mild and reversible increases in bilirubin (total, direct and indirect) were observed in TMC435 dose groups with no differences between 100 mg and 150 mg. There were no meaningful differences between treatment groups for any of the other laboratory parameters. There were no clinically significant findings on vital signs. Mean alanine aminotransferase (ALT) levels decreased in all treatment groups."