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Medivir Announces Positive 48-week Interim Data from TMC435 Hepatitis C Phase 2b ASPIRE Study in Treatment-Experienced Genotype-1 Patients

May 20, 2011

HUDDINGE, Sweden, May 20, 2011 /PRNewswire/ –

– All TMC435 Patient Subgroups Achieved Substantially Higher SVR4 Rates
(Undetectable Virus 4 Weeks After End of Treatment) Compared to
pegylated-interferon and ribavirin Alone

– TMC435 was Safe and Well Tolerated at All Doses and Treatment Durations

Medivir AB (OMX: MVIR), the emerging research-based specialty
pharmaceutical company focused on infectious diseases, today announced
results from the ASPIRE phase 2b study that evaluates the addition of once
daily TMC435 to pegylated interferon and ribavirin in patients with genotype
1 chronic hepatitis C whose prior treatment with pegylated-interferon
(PegIFN) and ribavirin (RBV) was unsuccessful either because they relapsed,
had a partial response or had a null response.

Bertil Samuelsson, CSO of Medivir, commented, “We are delighted with the
encouraging efficacy and safety results shown by TMC435-based triple therapy
over pegylated-interferon and ribavirin, in this 48-Week interim analysis of
the ASPIRE study in treatment experienced genotype-1 hepatitis C patients.
This patient group is known to be the most difficult one to treat, where in
particular prior null and partial responder groups respond very poorly upon
retreatment with PegIFN/RBV alone. With several global phase 3 clinical
trials ongoing in hepatitis C patients we are expecting the momentum to
continue with regards to the development of TMC435.”

ASPIRE (C206) – Design and Week-48 Interim Analysis

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 study includes patients that have relapsed, achieved
partial response, or achieved no response (null responders) to SoC treatment
and where 62 percent (287/462) of patients overall 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 1 of 7 different treatment arms: 6
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 PegIFN/RBV. PegIFN/RBV treatment was continued in all
patients until the study completion at week 48. This interim analysis was
performed when all patients had completed 48 weeks of treatment or
discontinued earlier. The analysis was done based on the intent-to-treat,
ITT, population which included all randomized subjects who took at least one
dose of the study medication. SVR4, Sustained Virologic Response 4 weeks
after planned end of treatment data, was available for 94% and 84% of TMC435
and placebo patients respectively.

ASPIRE Results – Efficacy

In this Week 48 interim analysis, all subgroups of treatment-experienced
patients who failed previous peginterferon and ribavirin treatment, achieved
substantially higher virologic response rates following treatment with
TMC435-containing regimen at all doses and durations, compared with
pegylated-interferon and ribavirin.

There was no relevant difference in virological response between the
TMC435 150 mg dose groups who received TMC435-based triple therapy of 12
weeks, 24 weeks or 48 weeks. At end of treatment (EoT) 92%, 83% and 71% of
relapser patients, partial responder patients and null responder patients
taking TMC435 150 mg once daily and placebo, respectively, achieved
undetectable HCV RNA levels compared to 70%, 17% and 25% in the placebo
PegIFN/RBV groups respectively. At week 4 after cessation of treatment (SVR4)
88%, 77% and 57% of prior relapser patients, partial responder patients and
null responder patients taking TMC435 150 mg once daily and placebo,
respectively, achieved undetectable HCV RNA levels, compared to 50%, 11% and
23% in the placebo groups, respectively.

        Virological Response Rates in TMC435 Dose Groups (150 mg q.d.) vs
                                     Placebo

                        TMC435     TMC435     TMC435   All TMC435   Placebo
         % (n/N)        12PR48     24PR48     48PR48      PR48       PR48
                         N=66       N=68       N=65      N=199       N=66

         Prior    EoT 92 (24/26) 93 (25/27) 92 (24/26) 92 (73/79) 70 (19/27)
      Relapser
                 SVR4 84 (21/25) 93 (25/27) 85 (22/26) 87 (68/78) 50 (12/24)

         Prior    EoT 78 (18/23) 83 (20/24) 86 (19/22) 83 (57/69)  17 (4/23)
       Partial
     Responder   SVR4 64 (14/22) 86 (18/21) 82 (18/22) 77 (50/65)  11 (2/18)

    Prior Null    EoT 65 (11/17) 71 (12/17) 77 (13/17) 71 (36/51)  25 (4/16)
     Responder
                 SVR4 56 (9/16)  60 (9/15)  56 (9/16)  57 (27/47)  23 (3/13)

q.d.: once daily; PR: pegIFNalpha-2A and ribavirin; EoT: End of Treatment,

SVR4: patients with undetectable HCV RNA (<25 IU/mL Undetectable) at EOT
and 4 weeks after planned EoT. Prior Relapser: undetectable HCV RNA at EoT
and detectable within 24 weeks of follow-up

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 8.3% of the subjects treated with TMC435 with
no substantial differences seen between the TMC435 dose groups. AEs leading
to treatment discontinuation were reported in 4.5% of the placebo subjects
and in 8.8% of the TMC435 treated subjects. 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 caused by 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
prior phase 2b PILLAR study of TMC435.

In the safety analyses, special attention was given to the following AEs
of interest: hepatobiliary AEs, pruritus, rash, anemia and cardiac events.
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 with TMC435 and PegIFN/RBV.

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, nor were there any relevant changes in
electrocardiogram (ECG) parameters, including QTc. Mean alanine
aminotransferase (ALT) levels decreased in all treatment groups.

About TMC435 in other clinical studies

TMC435 is a once-daily (q.d.) protease inhibitor drug jointly developed
by Tibotec Pharmaceuticals and, to treat chronic hepatitis C virus infections.

Three global clinical phase 3 response guided studies were recently
initiated by Tibotec:

– TMC435-C208 or QUEST-1 includes approximately 375 treatment-naive
patients

– TMC435-C216 or QUEST-2 includes approximately 375 treatment-naive
patients

– TMC435-C3007 or PROMISE includes approximately 375 who have relapsed
after prior interferon-based treatment

In parallel to the recent start of the global phase 3-studies, TMC435 is
currently in a follow up phase in three phase 2b clinical trials
(TMC435-C205, TMC435-C206 and TMC435-C215) in G1 treatment-naive and in G1
patients that failed previous IFN-based treatment. More safety and efficacy
data from the phase 2b trials will be presented at scientific meetings later
in 2011. Phase 3 programs for TMC435 are also ongoing in Japan.

For additional information for these studies, please see
http://www.clinicaltrials.gov

Conference call for analysts and investors:

There will be a conference call today, May 20 2011, for investors and
analysts at 08.00 (EDT) / 13.00 (GMT) / 14.00 (CET) to discuss the data. To
dial-in to the conference call please use the following numbers:

    Participant Telephone Numbers:   +1-718-354-1359      USA
                                     +46(0)8-5051-3785    Sweden
                                     +44(0)20-7136-2053   UK
    Participant code                 1156834

    Soundbyte Replay Access Number:  +44(0)20-7111-1244   UK
                                     +1-347-366-9565      USA
                                     +46(0)8-5051-3897    Sweden
    Replay Access Code:              1156834#

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.

About Medivir

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 protease inhibitor
which has recently entered phase 3 clinical development for hepatitis C and
is partnered with Tibotec Pharmaceuticals.

Medivir is also marketing its first product, the unique cold sore product
Xerese(TM)/Xerclear(R) which has recently been launched on the US market.
Xerese(TM)/Xerclear(R), which is also approved in Europe, is partnered with
GlaxoSmithKline to be sold OTC in Europe, Japan and Russia and with Meda AB
in North America, Canada and Mexico. Medivir has retained the Rx rights for
Xerclear(R) in Sweden and Finland.

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

    For more information about Medivir, please contact:

    Medivir (http://www.medivir.com):
    Rein Piir, CFO & VP Investor Relations         Mobile: +46-708-537-292
    Bertil Samuelsson, CSO Research & Development           +46-8-54683100

    M:Communications:
    Mary-Jane Elliott / Amber Bielecka / Katja Toon     +44(0)20-7920-2330
    Medivir@mcomgroup.com

    USA: Roland Tomforde                                   +1-212-232-2356

SOURCE Medivir AB


Source: newswire



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