Medivir: Results From a Phase IIa Study Evaluating Simeprevir and Sofosbuvir in Prior Null Responder Hepatitis C Patients Have

  Medivir: Results From a Phase IIa Study Evaluating Simeprevir and Sofosbuvir
  in Prior Null Responder Hepatitis C Patients Have Been Presented at CROI

Business Wire

HUDDINGE, Sweden -- March 6, 2013

Regulatory News:

Medivir AB (OMX: MVIR)

  *In an all-oral regimen of simeprevir and sofosbuvir 96.3 percent (26/27)
    and 92.9 percent (13/14) of patients in the 12-week arm with ribavirin and
    without ribavirin achieved sustained virologic response 8 weeks after the
    end of treatment (SVR8).
  *Once-daily all-oral simeprevir and sofosbuvir with or without ribavirin
    was generally well tolerated.

Medivir AB today announced that interim results from the COSMOS study
(Combination Of SiMeprevir and sOfosbuvir in HCV genotype 1 infected patientS)
have been presented at the 20th Conference on Retroviruses and Opportunistic
Infections (CROI) on March 6 in Atlanta, Georgia, USA.

These COSMOS interim results are from the first cohort of a phase IIa study of
the investigational protease inhibitor simeprevir (TMC435) administered once
daily with Gilead’s investigational nucleotide inhibitor sofosbuvir (GS-7977)
with and without ribavirin (RBV) for 12 and 24 weeks in genotype 1 prior
null-responder hepatitis C patients with mild to moderate fibrosis (METAVIR
F0-2). Simeprevir is jointly developed by Medivir AB and Janssen R&D Ireland,
an affiliate of the Janssen Pharmaceutical Companies.

At the time of the interim analysis, 26 out of 27 patients (96.3%) in the
12-week arm with RBV achieved SVR4 and 13 out of 14 patients (92.9%) in the
12-week arm without RBV achieved SVR4. A subsequent analysis confirmed that
all patients with SVR4 have also achieved SVR8. In the 24-week arms, SVR4
rates with RBV were 66.7% (one patient discontinued due to an AE and one
withdrew consent in this arm) and without RBV 100 percent. The number of
patients reaching this time point was limited, however.

The COSMOS regimen of once-daily simeprevir and sofosbuvir with or without
ribavirin was generally well tolerated and no serious adverse events occurred
during the treatment period.

“The COSMOS study specifically include hard-to-treat HCV patients, why the
high response rates seen so far in the study with simeprevir as part of an
interferon-free or interferon/ribavirin free combination regimen are very
encouraging,” says Charlotte Edenius, EVP of Research and Development, Medivir
AB.

COSMOS study Design

Cohort 1 of the randomized, open-label study investigates the efficacy and
safety of 12 or 24 weeks of simeprevir and sofosbuvir with or without
ribavirin (RBV) in HCV genotype 1 null responders to prior pegylated
interferon (IFN) and RBV therapy with METAVIR scores F0-F2.

Cohort 2, which has been fully enrolled to date, will investigate similar
regimens and durations in HCV genotype 1 prior null-responder and
treatment-naïve patients with METAVIR scores F3-F4.The study is being
conducted in the United States.

In total, 80 patients were randomized in Cohort 1. Sixty-one percent of
patients were male, 29 percent were African American, 25 percent were
Hispanic, 100 percent were prior null responders to pegylated interferon and
ribavirin, 75 percent had genotype 1a, and 94 percent were IL28B CT or TT
status. These characteristics represent a difficult-to-cure population.

COSMOS summary - efficacy:

In patients infected with HCV genotype 1 (including 1a) with a prior null
response to PegIFN/RBV, once daily SMV + SOF +/- RBV for 12 or 24 weeks
resulted in high SVR rates in this interim analysis as summarized.

Efficacy results with 150 mg simeprevir (SMV) and 400 mg sofosbuvir (SOF)
q.d. +/- ribavirin (RBV);
Patients n/N (%)     SMV + SOF     SMV + SOF     SMV + SOF     SMV + SOF
                      +RBV                          +RBV
                      24 weeks       24 weeks       12 weeks       12 weeks
                      (n=24)         (n=15)         (n=27)         (n=14)
RVR (week 4)          18/22          10/15          23/27          8/14
                      (81.8)         (66.7)         (85.2)         (57.1)
EoT*                  10/12          8/9 (88.9)     27/27 (100)    14/14
                      (83.3)                                       (100)
Relapse, n            0              0              1              1
SVR4                  4/6 (66.7)     5/5 (100)      26/27          13/14
                                                    (96.3)         (92.9)
SVR8                  4/6 (66.7)     5/5 (100)      26/27          13/14
                                                    (96.3)         (92.9)

q.d.: once daily; RVR: Rapid Viral Response; EoT: End of Treatment; SVR4 and
SVR8: patients with undetectable HCV RNA (* = Undetectable at EoT

COSMOS - Summary - Safety and Tolerability

The regimen of once-daily simeprevir and sofosbuvir with or without ribavirin
was generally well tolerated and no serious adverse events occurred during the
treatment period for the patients involved in the study. There were two
discontinuations due to an AE; 1 at least possibly related to study drug. Most
common Adverse Events were fatigue, headache, insomnia and nausea in >10%.
Anemia occurred only in subjects who received ribavirin. Grade 3/4 bilirubin
increases were infrequent, were not associated with increases in other liver
tests (AST, ALT, ALP, GGT), were only seen in patients who received ribavirin
and resolved when treatment was discontinued. Isolated Grade 3/4
amylase/lipase increases were observed but not associated with other
laboratory/clinical findings and were not confirmed on re-testing.

About the COSMOS Trial

COSMOS is a randomized, open-label study investigating the efficacy and safety
of 12 or 24 weeks of simeprevir and sofosbuvir with or without ribavirin in
HCV genotype 1 patients who are treatment naïve or have prior null response to
pegylated interferon and ribavirin therapy.

Cohort 1 of the COSMOS study enrolled 80 genotype 1 prior null-responder HCV
patients with METAVIR scores of F0-F2. Randomization was stratified by IL28B
status and genotype 1 subtype, into one of four arms including once-daily
simeprevir (150 mg) plus sofosbuvir (400 mg) for 24 weeks with or without
ribavirin, or once-daily simeprevir (150 mg) plus sofosbuvir (400 mg) for 12
weeks with or without ribavirin.

Cohort 2 of the study will investigate the same treatment regimens and
durations in genotype 1 prior null-responder and treatment-naïve patients with
METAVIR scores of F3-F4. The METAVIR score is used to quantify the degree of
inflammation and fibrosis of the liver. Liver fibrosis is scored on a
four-point scale.

About Simeprevir

Simeprevir, an investigational NS3/4A protease inhibitor jointly developed by
Janssen R&D Ireland and Medivir AB, is currently in late phase III studies as
a once-daily capsule (150 mg) taken in combination with pegylated interferon
and ribavirin for the treatment of genotypes 1 and 4 HCV.

Global phase III studies of simeprevir include QUEST-1 and QUEST-2 in
treatment-naïve patients, PROMISE in patients who have relapsed after prior
interferon-based treatment and ATTAIN in null-responder patients.In parallel
to these trials, phase III studies for simeprevir are ongoing in
treatment-naïve and treatment-experienced HIV-HCV co-infected patients, HCV
genotype 4 patients and Japanese HCV genotype 1 patients. Janssen
Pharmaceutical K.K. recently announced the submission of a new drug
application for simeprevir in Japan for the treatment of genotype 1 hepatitis
C.

Simeprevir is being studied in phase II interferon-free trials with and
without ribavirin in combination with:

  *Janssen’s non-nucleoside inhibitor TMC647055 and ritonavir in
    treatment-naïve genotype 1a and 1b HCV patients;
  *Gilead Sciences, Inc.’s nucleotide inhibitor sofosbuvir (GS-7977) in
    treatment-naïve and previous null-responder genotype 1 HCV patients; and
  *Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir
    (BMS-790052) in treatment-naive and previous null-responder genotype 1 HCV
    patients.

In addition, Janssen Pharmaceutical Inc. recently announced that it has
entered into a non-exclusive collaboration with Vertex Pharmaceuticals to
evaluate in a phase II study the safety and efficacy of an all-oral regimen of
simeprevir and Vertex’s investigational nucleotide analogue polymerase
inhibitor VX-135 for the treatment of HCV. As a first step, Janssen
Pharmaceutical Inc. will conduct a drug-drug interaction (DDI) study with
simeprevir and VX-135. Janssen Pharmaceutical Inc. also recently announced
plans to initiate a phase IIa trial of an investigational interferon-free
regimen with simeprevir, TMC647055 and Idenix’s IDX719, a once-daily NS5A
inhibitor, with and without ribavirin.

For additional information about simeprevir clinical trials, please visit
www.clinicaltrials.gov.

About Sofosbuvir

Sofosbuvir (formerly referred to as GS-7977) is a once-daily nucleotide analog
polymerase inhibitor for the treatment of HCV infection being developed by
Gilead Sciences. Sofosbuvir is being evaluated as part of multiple therapeutic
regimens, including programs with RBV alone and in combination with peg-IFN
and RBV.

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause
of chronic liver disease and liver transplants, is a rapidly evolving
treatment area with a clear need for innovative treatments. Approximately 150
million people are infected with hepatitis C worldwide, and 350,000 people per
year die from the disease.

About Medivir AB

Medivir is an emerging research-based pharmaceutical company focused on
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 simeprevir, a novel protease
inhibitor in late phase III clinical development for hepatitis C that is being
developed in collaboration with Janssen R&D Ireland. Medivir has also a broad
product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website:
www.medivir.com

This information was brought to you by Cision http://news.cision.com

Contact:

Medivir AB
Rein Piir
EVP Corporate Affairs & IR
Mobile: +46 708 537292
 
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