Medivir updates investors on Hepatitis C programs...

Medivir offers an update on it's HCV development projects including the phase IIb trials for it's once daily. HCV protease inhibitor TMC435 and the early development programs for it's HCV nucleoside and a nucleotide inhibitors. For TMC435: results from the PILLAR trial looking at TMC435 + P/R in treatment naive genotype 1 subjects found 81-86% of patients achieved SVR24, compared to 65% in the placebo + P/R arm. A majority of patients (86%) in the TMC435 treatment arms had a shortened treatment duration of treatment (24 weeks), compared to a 48 weeks in the placebo + P/R arm. For the ASPIRE trial, looking at TMC435 + P/R in partial and null responders to previous treatment. The TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to the control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders. Other interesting notes include a change in primary endpoint from SVR24 to SVR12 in the TMC435 Phase III trials; a Phase III TMC435 + P/R vs Telaprevir + P/R in nonresponders yet to be started; an interferon-free, combination trial looking at TMC435 + Pharmasset's PSI-7977 with and without ribavirin in genotype 1 non-responders. We're likely to see more companies pair combinations of drugs as the 2nd and 3rd generation DAAs move forward in development and others are abandoned due to inferior efficacy and/or side effect issues.

Medivir: Key News from the Ongoing Capital Markets Day

HUDDINGE, Sweden, Nov 15, 2011 (BUSINESS WIRE) -- Regulatory News:

Medivir AB, a research-based speciality pharmaceutical company focused on infectious diseases, reports the following key news concerning their hepatitis C projects.

Medivir programmes in collaboration with Tibotec Pharmaceuticals Medivir and Tibotec Pharmaceuticals have two programmes for the development of antiviral therapies for future treatment of hepatitis C (HCV), these are based on the HCV protease and polymerase drug targets.

In the protease project, TMC435 is in global phase III development in both treatment naive and in patients that have relapsed after previous treatment with pegylated interferon (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C genotype 1.

The HCV polymerase collaboration program consists of two early development projects, a nucleoside and a nucleotide inhibitor.

TMC435 (NS3/4A protease inhibitor) presently in development in Hepatitis C genotype 1 infected patients.

Phase IIb studies Final SVR24 data from the phase IIb study PILLAR, in treatment-naive patients, was presented last week at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, CA, USA. Results from this final PILLAR analysis showed that TMC435 administered in combination with peginterferon a-2a and ribavirin (PR) resulted in significantly higher sustained virologic response (SVR) rates compared to placebo plus PR, with the majority of TMC435 patients able to shorten total treatment duration to 24 weeks based on response-guided therapy.

-- In the 150 mg TMC435 treatment groups, 81-86 percent of patients achieved SVR24, compared to 65 percent of patients treated in the placebo arm. In addition, 86 percent of patients in the TMC435 treatment arms had a shortened treatment duration of 24 weeks, compared to a 48 weeks treatment duration for patients who received placebo plus P/R.

-- The once daily dosed TMC435 was generally safe and well tolerated at all doses and treatment durations.

Medivir recently issued a press release on final results from phase IIb study ASPIRE This trial evaluated TMC435 once daily in addition to pegylated interferon (PegIFN) and ribavirin (RBV) in patients with 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 to those retreated with pegylated-interferon and ribavirin alone.

-- All TMC435 subgroups achieved substantially higher viral cure rates (SVR24) compared to control group (PegIFN and RBV alone): 85% vs. 37% in prior relapsers, 75% vs. 9% in prior partial responders and 51% vs. 19% in prior null responders.

-- The once daily TMC435 was generally safe and well tolerated at all doses and treatment durations. Phase III studies

SVR12 - new endpoint

-- In the ongoing phase III studies in naive and patients that have relapsed following previous treatment, the primary endpoint has been changed from SVR24 to SVR12 following recent discussions with the FDA. These studies (QUEST 1 &2 and PROMISE) were all fully recruited in August.

Phase III study in non-responder patients to be initiated

-- Phase III study in prior partial and null responder HCV genotype 1 patients will start within six months. This study will evaluate efficacy, safety and tolerability for TMC435 vs telaprevir in combination with PegINFa-2a and Ribavirin in chronic Hepatitis C patients.

Phase II interferon free combination study with TMC435 and PSI-7977

-- This interferon free phase II combination study will commence shortly. It will evaluate TMC435 and PSI-7977 in combination with and without ribavirin for 12 and 24 weeks in genotype 1 patients who had a prior null response to Peg-IFN/RBV. The study design is now posted on www.clinicaltrials.gov .

HCV polymerase collaboration

TMC649128 TMC649128, the first NS5B nucleoside polymerase inhibitor under the collaboration, entered into clinical development in Q1-2011. It was safe and well tolerated at all doses tested for up to 14 days. However the antiviral activity failed to meet the target product profile and therefore the clinical development has now been discontinued.

Nucleotide program The focus of HCV polymerase collaboration is now on a liver targeted nucleotide polymerase inhibitor program. A clinical candidate has been selected and the project is now in preclinical development stage.

Capital Markets Day Presentation The presentation from this research & development update is available on our website under the heading Investor Relations / Latest Events.

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

This information was brought to you by Cision http://www.cisionwire.com

SOURCE: Medivir

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

I need to add 'SVR4' to my list of HCV Direct Acting Antiviral terminology... 'SVR4' is SVR 4 weeks post end of treatment date. Glad to get that squared away. This press release covers the majority of results of the phase IIb trial (ASPIRE) with the HCV protease inhibitor TMC435 looking at those who were previous non-responders to previous Peg-inf + P/R therapy - Relapsers, Partial Responders and Null-Responders to be specific. SVR4 in the TMC435 150mg + P/R was achieved in 88%, 77% and 57% oof those respective populations vs 50%, 11% and 23% in the placebo + P/R ar, again, respectively. No relevant differences between the 12, 24 and 48 week arms. Serious AEs were reported in 6.1% subjects in the placebo and vs 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. The relative lack of AE's compared to the first generation of HCV PIs and the once a day dosing make TMC435 one to keep our eyes on.

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