Medivir AB (OMX: MVIR), the emerging research-based specialty pharmaceutical company focused on infectious diseases announces today positive top-line 24-week interim data from the Phase 2b ASPIRE (C206) study of TMC435 in treatment-experienced hepatitis C patients. The results demonstrate the potent and consistent antiviral efficacy of TMC435 in patients who had failed earlier treatment with peg-IFN and ribavarin (standard of care), as well as an safety and adverse event profile for TMC435 that is consistent with what we have previously reported in the phase 2b PILLAR C205 study. TMC435, a hepatitis C protease inhibitor, dosed once daily (q.d.) is being developed jointly by Tibotec Pharmaceuticals and Medivir.
The ASPIRE study evaluates the effect of TMC435 in combination with standard of care in 462 patients infected with the difficult to treat genotype-1 hepatitis C virus who had undergone and failed prior treatment with standard of care. The study includes patients that have relapsed, achieved partial response, or achieved no response (null responders) to treatment with standard of care.
TMC435 was administered once daily at a dose of either 100 mg or 150mg given for either 12, 24, or 48 weeks in combination with standard of care. Standard of care treatment was continued until the study completion at week 48.
Overview of the ASPIRE (C206) Week 24 Interim Study Results
The week 24 interim analysis was performed when all patients completed 24 weeks of treatment or discontinued earlier. An Intention-to-Treat, ITT, analysis was performed including all patients who took at least one dose of TMC435.
In the interim analysis patients treated with TMC435 and standard of care demonstrated high response rates and antiviral efficacy in all patient groups up to and including week 4, 12 and 24.
In the relapser group 81%, 92% and 94% of patients taking TMC435 and Peg-IFN and RBV achieved undetectable HCV RNA levels at week 4, week 12 and week 24 respectively. For the partial responder group 62%, 84% and 86% achieved undetectable HCV RNA levels at week 4, week 12 and week 24 respectively.
The null responder group also demonstrated significant response rates with 38%, 64% and 78% of patients taking TMC435 and Peg-IFN and RBV achieving undetectable HCV RNA levels at week 4, week 12 and week 24 respectively. All patients continue on active treatment up until week 48.
In the table below the TMC435 data pooled and all data are taken into account at the specific time point.
An Intention-to-Treat analysis of Virologic Response: HCV RNA<25IU/mL undetectable
Safety and Tolerabillty
An Intention-to-Treat analysis was performed including all patients who took at least one dose of TMC435. TMC435 was generally safe and well tolerated and the results were consistent with the previously reported phase 2b PILLAR C205 study. Significant decreases in transaminases (ALT and AST) were observed in all TMC435 treatment groups. The two most frequently reported AEs were fatigue and headache, with comparable results shown from the placebo group.
Commenting on the results, Ron Long, CEO of Medivir said, "We are extremely encouraged and excited by the pronounced efficacy and advantageous safety of TMC435 in these difficult-to-treat patients that are in a great need of new and improved treatment options. We are now looking forward to the next important development milestone for TMC435, the start of phase 3 clinical trials in treatment-naïve patients in early 2011."
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