On Friday, October 26, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Gilead’s nucleotide analogue reverse transcriptase inhibitor, tenofovir disoproxil fumarate (brand name, Viread). The labeling requested was for the “treatment of HIV-1 infection in combination with other antiretroviral medicines.” Tenofovir is the first nucleotide analog approved for the treatment of HIV infection, and Gilead’s second such product. Adefovir (trade name Preveon) was turned down by the FDA in late 1999 due to safety concerns and lackluster clinical results. Nucleotide analogue reverse transcriptase inhibitors (NtRTIs) are similar to nucleoside analogue RTIs and block HIV replication in the same manner. The difference is that nucleotide analogues already have one phosphate group attached.
The FDA based its approval of tenofovir on the results of two clinical studies, study 907 and study 902, involving more than 700 patients who had previously been treated with antiretroviral agents but showed signs of treatment failure. Study 907 is a 552-patient, 48-week placebo-controlled, treatment intensification study. Twenty-four week results were presented to the FDA. Study 902 is a smaller study, also in treatment experienced individuals, that compares treatment intensification with three different doses of tenofovir or placebo. Study volunteers who received tenofovir showed a mean viral load reduction of 0.62 logs compared to individuals who received a placebo with the standard antiretroviral regimen. Tenofovir is available as a 300 mg tablet to be taken orally, with a meal.
Because the approval of tenofovir was based on clinical trials involving individuals previously treated with antiretrovirals, the risk-benefit ratio for untreated individuals has yet to be determined. Furthermore, there are no study results to show long-term inhibition of the clinical progression of HIV by tenofovir. Additional studies under way are expected to address these issues: Study 903 enrolled nearly 600 treatment naive individuals and is expected to produce results by mid-2002; Study 910, a roll-over extension study of individuals from studies 902 and 907, will examine long-term efficacy and safety issues.