Medivir Announces Final Results from TMC435 Phase IIb ASPIRE (C206) Study
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
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.
Sustained Virologic Response (SVR24) Rates in TMC435 Dose Groups (150 mg q.d.) vs Placebo All TMC435 TMC435 TMC435 TMC435 Placebo 12PR48 24PR48 48PR48 PR48 PR48 % (n/N) N=66 N=68 N=65 N=199 N=66 76.9 88.9 88.5 84.8 37.0 Relapsers SVR24 (20/26) (24/27) (23/26) (67/79) (10/27) Partial 65.2 75.0 86.4 75.3 8.7 Responders SVR24 (15/23) (18/24) (19/22) (52/69) (2/23) Null 52.9 41.2 58.8 51.0 18.8 Responders SVR24 (9/17) (7/17) (10/17) (26/51) (3/16)
q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of
SVR24: patients with undetectable HCV RNA (<25 IU/mL Undetectable) 24
weeks after planned EoT. All TMC435 groups: p<0.001 vs placebo. Prior
Relapser: undetectable HCV RNA at EoT and detectable within 24 weeks of
Prior Partial Responders: more than 2 log reduction in HCV RNA at W12
but not achieving undetectable at EoT
Prior Null Responders: less than 2 log reduction in HCV RNA at W12
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-naive hepatitis C patients of
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.
DRAGON (C215) – Update on recently published results
The final data from the phase II Dragon study in Japan was recently
published at the Japan Digestive Disease Week meeting, 20-23 October 2011 in
Fukuoka, Japan. The DRAGON study is a phase II randomized, open-label,
response-guided study to evaluate the efficacy, safety, and pharmacokinetics
of TMC435 plus PegIFN/RBV in 92 Japanese treatment-naive patients infected
with HCV genotype-1.
Addition of once daily TMC435 (100 mg) to PegIFN/RBV increased the viral
cure rate (SVR24) from 46% in the PegIFN/RBV only group to 82% (32/39) in
the TMC435 100mg groups. In these groups, 87% of patients were eligible to
complete all treatment at Week 24 if preset criteria on virologic response
were met. TMC435 was generally safe and well tolerated with no apparent
difference in the safety profile between TMC435 treatment groups and the
control group (PegIFN/RBV only).
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-naive 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.
For additional information from these studies, please see
http://www.medivir.com and http://www.clinicaltrials.gov
Conference call for analysts and investors:
There will be a conference call today, 2 November 2011, for investors
and analysts at 11.00 (EDT) / 15.00 (GMT) / 16.00 (CET) to discuss the data.
To dial-in to the conference call please use the following numbers:
Participant telephone numbers: Sweden +46 (0)200 884 518 Europe +44 (0)1452 569 335 USA +1 866 655 1591 Please quote participant code 23849230 Soundbyte replay access numbers: Sweden +46 (0)200 899 157 Europe +44 (0)1452 55 00 00 USA +1 866 247 4222 Replay access code: 23849230#
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and is a
leading cause of chronic liver disease and liver transplants. The WHO
estimates that nearly 180 million people worldwide, or approximately 3% of
the world’s population, are infected with hepatitis C virus (HCV). The CDC
has reported that almost three million people in the United States are
chronically infected with HCV.
Medivir is an emerging research-based specialty pharmaceutical company
focused on the development of high-value treatments for infectious diseases.
Medivir has world class expertise in polymerase and protease drug targets
and drug development which has resulted in a strong infectious disease R&D
portfolio. The Company’s key pipeline asset is TMC435, a novel protease
inhibitor that is in phase III clinical development for hepatitis C and is
partnered with Tibotec Pharmaceuticals.
In June 2011, Medivir acquired the specialty pharmaceutical company
BioPhausia to ensure timely commercialization of TMC435 in the Nordic
markets, once approved.
Medivir’s first product, the unique cold sore product Xerese(R)/Xerclear(
R), was launched on the US market in February 2011. Xerese(R)/Xerclear(R),
which has been approved in both the US and Europe is partnered with
GlaxoSmithKline to be sold OTC in Europe, Japan and Russia. Rights in North
America, Canada and Mexico were sold to Meda AB in June 2011. Medivir has
retained the Rx rights for Xerclear(R) in Sweden and Finland.
For more information about Medivir, please visit the Company’s website:
For more information about Medivir, please contact: Medivir (http://www.medivir.com) Rein Piir, EVP Corporate Affairs & IR Mobile: +46-708-537-292 M:Communications Europe: Peter Laing, Amber Bielecka Medivir@mcomgroup.com +44(0)20-7920-2330 USA: Roland Tomforde +1-212-232-2356