Tenofovir Alafenamide

(S)-Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate

http://www.ama-assn.org/resources/doc/usan/tenofovir-alafenamide.pdf

Gilead Sciences, Inc.on January 24, 2013 announced the initiation of the first of two Phase 3 clinical trials (Study 104) evaluating a single tablet regimen containing tenofovir alafenamide (TAF) for the treatment of HIV-1 infection in treatment-naïve adults. TAF is a novel prodrug of tenofovir, the active agent in Viread^® (tenofovir disoproxil fumarate). The Phase 3 studies will examine a once-daily single tablet regimen of TAF 10 mg/elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg compared to Gilead’s Stribild^® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among patients new to HIV therapy. The second Phase 3 study (Study 111) will be initiated later this quarter.

We are pleased to move TAF into Phase 3 clinical research,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “We believe that TAF’s smaller milligram size has the potential to offer safety and tolerability advantages over existing therapies, and may enable the creation of new single tablet regimens for HIV.”

In October 2012, Gilead announced topline results from a Phase 2 study comparing the TAF/elvitegravir/cobicistat/emtricitabine single tablet regimen to Stribild. The study found that the TAF-based regimen met its primary objective based on the proportion of patients with HIV RNA (viral load) levels < 50 copies/mL at 24 weeks of therapy. In addition, statistically significant differences in bone and renal safety were observed between the two arms in favor of the TAF-containing regimen. Both the type and frequency of laboratory abnormalities and adverse events were otherwise comparable between study arms. Full results from the Phase 2 study will be presented at an upcoming medical conference.

Stribild was approved by the U.S. Food and Drug Administration (FDA) in August 2012 and is Gilead’s third single tablet regimen for HIV. A marketing application for Stribild is currently pending in Europe.

Tenofovir alafenamide fumarate (TAF), or GS 7340, is a nucleotide reverse transcriptase inhibitor and a novel prodrug of tenofovir. It is under development by Gilead Sciences for use in the treatment of HIV infection. Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (Viread), TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent.^[1][2] Gilead has announced a phase 3 clinical trial evaluating a single-tablet regimen combining GS-7340 with cobicistat, emtricitabine and elvitegravir^[3] and plans to coformulate the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.^[4][5][6] In a 48 week study comparing Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate toelvitegravir/cobicistat/emtricitabine/GS 7340, the results showed the prodrug to be non inferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function.^[7]

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