Medivir Announces Phase 2b 24-week Interim Results of TMC435 in Treatment-naïve Patients Chronically Infected with Genotype-1 Hepatitis C Virus

Medivir Announces Phase 2b 24-week Interim Results of TMC435 in
Treatment-naïve Patients Chronically Infected with Genotype-1 Hepatitis
C Virus

Potent and consistent antiviral efficacy was demonstrated at 24-week
end-of-treatment and in interim SVR4 and SVR12 results. There were no
clinically relevant differences between TMC435 treatment groups and
placebo for adverse events.

Medivir announced today 24-week end-of-treatment interim results from
the 5-arm phase 2b response guided PILLAR study in 386 treatment-naïve
patients with hepatitis C virus (HCV) genotype-1 (TMC435-C205). 

TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec
Pharmaceuticals, dosed as one pill once daily (q.d.) to treat hepatitis
C virus infections (HCV). 

In the PILLAR study, 75mg or 150mg TMC435 was given for either 12 weeks
or 24 weeks in combination with 24 weeks of ribavirin and
pegIFNalpha-2A, the current standard of care (SOC). Patients stopped all
treatment at week 24 when HCV RNA levels at week 4 were < 25 log10 IU/mL
detectable or undetectable and HCV RNA levels at week 12, week 16 and
week 20 were < 25 log10 IU/mL undetectable. Patients who did not meet
the above response-guided criteria continued with SOC until week 48. The
results showed that in the TMC435 treatment groups  83% of patients were
able to stop all therapy at Week 24.  

Potent and consistent antiviral efficacy was demonstrated at 24-week
end-of-treatment and in interim SVR4 and SVR12 rates with no major
differences between TMC435 doses or length of triple therapy. 92% of
patients taking TMC435 and Peg-IFN/RBV (SoC) achieved undetectable HCV
RNA levels at week 4 and 92% at week 12 after cessation of treatment,
i.e. SVR4 and SVR12. SVR4 and SVR12 data were available for 82% and 42%
of the TMC435-treated patients respectively who had stopped all therapy
before or at Week 24 and had completed the follow-up visits. Both the
viral breakthrough rate (4.9%) and relapse rate (1.6%) were low in the
TMC435 treatment groups. 

TMC435 was generally safe and well tolerated with no relevant
differences in adverse events (AEs) between placebo and TMC435 treatment
groups. Most AEs were mild to moderate in severity and the
discontinuation rate due to AEs was low and not different from placebo. 

When looking at particular adverse events of interest, the incidence of
rash, pruritis, GI side effects and anemia were similar in TMC435 groups
and placebo and were generally mild to moderate in nature. Use of
erythropoetin-stimulating agents (ESAs) was not allowed during the
trial. 

In laboratory parameters, there were no clinically relevant differences
between any TMC435 groups and placebo except for mild bilirubin
elevations. Significant decreases in transaminases (ALT and AST) were
observed in all treatment groups. 

Further safety and efficacy data will be presented at future scientific
meetings later in 2010. 

"We are extremely encouraged and excited by the efficacy and safety
demonstrating that TMC435 is truly a second-generation HCV protease
inhibitor," stated Bertil Samuelsson, CSO of Medivir. "We also are
looking forward to the top-line data coming up from the phase 2b trial
C206 (ASPIRE) in treatment-experienced patients later this year as well
as start of phase 3 clinical trials in treatment-naïve patients early
next year.” 

Frequency of Undetectable* HCV RNA Levels During and After Treatment  
Treatment week   TMC12PR2475mg q.d.   TMC24PR2475mg q.d.  
TMC12PR24150mg q.d.   TMC24PR24150mg q.d.   SoC  
N (%)            N=78                 N=75                 N=77         
        N=79                  N=77
Week-24, EoT***  67/73 (92%)          65/67 (97%)          68/74 (92%)  
        73/78 (94%)           4/18 (22%)**
Follow-up at Week-4 and Week-12 after EoT
SVR4             59/65 (91%)          56/60 (93%)          57/61 (93%)  
        63/68 (93%)           NA****
SVR12            32/33 (97%)          27/29 (93%)          32/36 (89%)  
        29/32 (91%)           NA

* < 25 log10 IU/mL undetectable
** End of treatment
***EoT: End of Treatment
**** Patients in the control arm continue SoC till Week 48 and SVR data
are not available
q.d.: once daily, PR: pegIFNalpha-2A and ribavirin, SVR4: undetectable
HCV RNA at EoT & undetectable HCV RNA 4 weeks after planned EoT, SVR12:
undetectable HCV RNA at EoT & undetectable HCV RNA 12 weeks after
planned EoT 

About TMC435 clinical trial programs
TMC435 is a protease inhibitor jointly developed by Medivir and Tibotec
Pharmaceuticals to treat hepatitis C virus infections (HCV). 

TMC435 is currently being developed 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. Safety and
efficacy data from the phase 2b trials will be presented at scientific
meetings later in 2010. 

TMC435-C205 is a global phase 2b study in 386 genotype-1 treatment-naïve
patients. It is a once daily treatment of TMC435 with different doses
and durations given in addition to standard of care treatment,
consisting of ribavirin and pegIFNalpha-2A. 

TMC435-C215 is a Japan phase 2b study in 92 genotype-1 treatment-naïve
patients. It is a once daily treatment of TMC435 with different doses
and durations given in addition to standard of care treatment,
consisting of ribavirin and pegIFNalpha-2A. 

TMC435-C206 is a global phase 2b study in 463 genotype-1
treatment-experienced patients. It is a once daily treatment of TMC435
in with different doses of given in addition to standard of care
treatment, consisting of ribavirin and pegIFNalpha-2A. 

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. 

Invitation to a Press Conference
Medivir will host a teleconference today at 15:00 (Central European
summer time) focusing on the phase 2b 24-week interim results.
To participate in the teleconference, please call +46 8 619 75 30 using
the participant code 195272#. 

For additional information, please contact
Rein Piir, CFO & VP Investor Relations, Medivir; +46 8 54683123 or
+46 708 537 292. 

For more information on Medivir, please see the company website:
www.medivir.se (http://www.medivir.se)