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


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

-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

Huddinge, Sweden - 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
% (n/N)                        TMC435      TMC435      TMC435      All  
      Placebo
                               12PR48      24PR48      48PR48     
TMC435      PR48
                               N=66        N=68        N=65        PR48 
      N=66
                                                                   N=199
Prior Relapser           EoT   92 (24/26)  93 (25/27)  92 (24/26)  92
(73/79)  70 (19/27)
                         SVR4  84 (21/25)  93 (25/27)  85 (22/26)  87
(68/78)  50 (12/24)
Prior Partial Responder  EoT   78 (18/23)  83 (20/24)  86 (19/22)  83
(57/69)  17 (4/23)
                         SVR4  64 (14/22)  86 (18/21)  82 (18/22)  77
(50/65)  11 (2/18)
Prior Null Responder     EoT   65 (11/17)  71 (12/17)  77 (13/17)  71
(36/51)  25 (4/16)
                         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-naïve
patients
  · TMC435-C216 or QUEST-2 includes approximately 375 treatment-naïve
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-naïve 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
www.clinicaltrials.gov (Local%20Settings/chaede.MEDIVIR/AppData/Local/Mi
crosoft/Local%20Settings/Temporary%20Internet%20Files/Local%20Settings/A
ppData/Local/Local%20Settings/Temporary%20Internet%20Files/Users/E020454
/AppData/Local/Microsoft/Windows/E020454/AppData/Local/Microsoft/Documen
ts%20and%20Settings/bhvam/Local%20Settings/Temporary%20Internet%20Files/
Local%20Settings/Temporary%20Internet%20Files/OLK5B/www.clinicaltrials.g
ov)

For more information about Medivir, please contact:

Medivir (www.medivir.com (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
ToonMedivir@mcomgroup.com (Medivir@mcomgroup.com)     +44(0)20 7920 2330
USA: Roland Tomforde                                                    
                                         +1 212-232-2356

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™/Xerclear® which has recently been launched on the US
market.  Xerese™/Xerclear®, 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® in Sweden and Finland.

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

 

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