quarta-feira, janeiro 11, 2006
Tibotec procura aprovação da EMEA para TMC114
11-01-2006 14:30CORK, Ireland, January 11 /PRNewswire/ ---
Follows Recent Submission of New Drug Application to the US FDA
Tibotec Pharmaceuticals Ltd. announced today that it has submitted an application for marketing authorisation for TMC114, an investigational protease inhibitor for the treatment of HIV-1 infected patients, to the European Agency for the Evaluation of Medicinal Products (EMEA). This submission was completed one week after the submission of a New Drug Application for TMC114 to the United States Food and Drug Administration, which the company announced in December.
Both submissions are based on the efficacy and safety results of the 24-week dose-finding phase of two Phase IIb randomized controlled studies, known as POWER 1 and POWER 2, and supportive data from a non-randomized open label trial, POWER 3. Based on the data from these studies, the submissions to the FDA and EMEA recommend a dose of 600 mg of TMC114 boosted with 100 mg ritonavir twice daily for treatment-experienced patients.
The POWER 1 data were presented at the International AIDS Society (IAS) conference in Rio de Janeiro in July 2005; the POWER 2 data were presented at the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in December 2005 in Washington D.C. Both studies were randomized trials of TMC114 boosted with ritonavir (TMC114/r) in patients with experience of at least 1 PI, 1 NNRTI and 1 NRTI and who had 1 or more primary PI mutations. Patients were randomized to receive optimized background regimen (OBR) plus one of four doses of TMC114/r (400mg/100mg QD; 800mg/100mg QD; 400mg/100mg BID; 600mg/100mg BID) or OBR plus investigator-selected control PI(s).
The POWER 1 results showed that 77% of patients achieved a reduction in viral load (plasma HIV RNA) of 1 log10 or more in the highest TMC114/r dose group, 600mg/100mg BID, compared to 25% in the control group. The most common treatment-emergent adverse events (AEs) in the TMC114/r arms were headache (17%) and diarrhea (16%) compared with 24% and 29% respectively in the control arm. Overall, 14% of both TMC114/r and control patients reported at least one serious AE (SAE).
In patients with more advanced disease, the POWER 2 results showed that 62% of patients achieved a reduction in viral load (plasma HIV RNA) of 1 log10 or more in the highest TMC114/r dose group, 600mg/100mg BID, compared to 14% in the control group. The most common treatment-emergent AEs were headache and nausea, which were each 17% across all TMC114/r arms compared with 17% and 9% respectively in the control arm. Overall, 15% of TMC114/r and 8% of control patients reported at least one SAE.
TMC114, boosted with low-dose ritonavir, is currently in pivotal Phase III clinical trials in both treatment-experienced and treatment-naïve HIV-1 infected patients. The TMC114-C214 trial, for moderately treatment-experienced patients, is investigating a dose of 600 mg of TMC114 boosted with 100 mg of ritonavir twice daily. The TMC114-211 trial, for treatment-naïve patients, is currently recruiting; the study will investigate a dose of 800 mg of TMC114 boosted with 100 mg of ritonavir once daily.
Pending regulatory approval, Tibotec Therapeutics will commercialize the product in the U.S. and Tibotec, a division of Janssen-Cilag, will commercialize the product in Europe and other countries. The trade name for the marketed product has not yet been determined.