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By Rob Camp

May 25, 2006

Darunavir (DRV) is a ritonavir(r)-boosted protease inhibitor that has been studied for use in heavily treatment-experienced patients. In the future, DRV/r will be evaluated for use in less-experienced, treatment-naïve and pediatric populations. The current New Drug Application, and this paper, deal only with Tibotec/Johnson & Johnson (J&J), the sponsor’s, current application for accelerated approval for darunavir (formerly known as TMC-114, brand name Prezista®) among heavily treatment-experienced individuals, based on data from the POWER studies.

Development of DRV was spectacularly fast. In fact, before data from efficacy studies were presented publicly anywhere, the sponsor had agreed with FDA to rev up the research program by enrolling more people into an agreed-upon dose, and present it for approval well ahead of schedule. The last time phase IIB data was encouraged by FDA as basis of an approval package was for indinavir in 1996.

Darunavir/r has a standard second-generation PI safety profile. The most commonly reported adverse events across all clinical trials include diarrhea, nausea, fatigue, headache and vomiting. The most common laboratory abnormalities were elevated liver enzymes, triglycerides and lipids.

DRV/r is more bioavailable after a meal, and will be recommended to be administered with food. The dose to be marketed is 600mg DRV + 100mg /r BID.

Twenty-four week data are available from two studies, POWER-1 and -2, in 131 patients, and limited information on 327 others who were enrolled into an open label Phase III cohort (POWER-3) that allows FDA to see data on 458 people with advanced disease (< 200 CD4s) at 24 weeks. TAG regrets the lack of a public FDA Antiviral Drug Advisory Committee hearing to discuss the implications of approving a drug with so little public and comparative data. TAG and the undersigned organizations believe that FDA should approve Tibotec’s application for accelerated approval of Prezista® brand DRV/r to treat advanced HIV infection in treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This recommendation is based on the follow-up studies in section 2 being commenced and successfully completed in a timely fashion.

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