Gilead’s once-daily novel prodrug for the treatment of HIV meets 24-week primary objective in Phase 2 study

Gilead Sciences, Inc. (Nasdaq: GILD) today announced that a Phase 2 clinical trial evaluating tenofovir alafenamide fumarate (TAF; formerly referred to as GS-7340), an investigational novel prodrug of tenofovir for the treatment of HIV-1 infection, met its primary objective. The ongoing study compares a once-daily single tablet regimen containing TAF 10 mg/elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg with StribildTM (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among treatment-naïve adults. The TAF-based regimen achieved a similar virologic response to Stribild based on the proportion of patients with HIV RNA levels (viral load) of less than 50 copies/mL at 24 weeks of therapy (87 percent versus 90 percent, respectively).

Compared to Stribild, the TAF-based regimen demonstrated statistically significantly smaller reductions from baseline to week 24 in bone mineral density at the lumbar spine and hip (p<0.005). In addition, small, statistically significant differences were seen in serum creatinine and in calculated creatinine clearance between the two arms in favor of the TAF-containing regimen (p<0.02). No patient discontinued study drug for renal adverse events. There were no statistically significant differences in the frequency of laboratory abnormalities and the frequency and nature of adverse events were generally similar between the two arms. Both regimens were generally well tolerated. Gilead plans to submit these data for presentation at a scientific conference next year.

“These interim findings are encouraging and warrant advancing this TAF-containing single tablet regimen into Phase 3 development,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences.

TAF is also being studied in a second ongoing Phase 2 trial evaluating a single tablet regimen containing TAF, Janssen R&D Ireland’s protease inhibitor Prezista® (darunavir), cobicistat and emtricitabine compared to Truvada® (emtricitabine and tenofovir disoproxil fumarate) plus Prezista and cobicistat, dosed as individual components. The study is fully enrolled and 24-week results will be available in the first half of 2013.

About the Study

The Phase 2 study is a randomized, double-blind 48-week clinical trial among HIV-1 infected adults with HIV RNA levels (viral load) greater than or equal to 5,000 copies/mL and CD4 cell counts greater than 50 cells/mm3. A total of 170 patients were randomized (2:1) to receive a once-daily tablet containing TAF 10 mg/elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg (n=112) or Stribild (n=58). Bone mineral density was assessed in all patients by DEXA scans at baseline and at week 24.

The study is ongoing. Secondary endpoints will include the proportion of patients who achieve viral load of less than 50 copies/mL at 48 weeks of therapy, and changes in HIV-1 RNA and in CD4 cell count from baseline to Weeks 24 and 48. After week 48, patients will continue to take their blinded study drug until treatment assignments have been unblinded, at which point all will be given the option to participate in an open-label rollover extension and receive the TAF-based single tablet regimen.

Additional information about the study can be found at www.clinicaltrials.gov.

About Tenofovir Alafenamide Fumarate

Tenofovir alafenamide fumarate (TAF) is a nucleotide reverse transcriptase inhibitor and a novel prodrug of tenofovir, the active agent in Viread® (tenofovir disoproxil fumarate). Phase 1b dose-ranging studies identified a dose of TAF that is ten times lower than Viread and provides greater antiviral efficacy. The smaller milligram size of TAF may enable the development of new fixed-dose combinations and single tablet regimens for HIV therapy that are not feasible with Viread.

About Elvitegravir

As an integrase inhibitor, elvitegravir interferes with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead’s agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights. Gilead submitted a New Drug Application (NDA) to FDA for elvitegravir on June 27, 2012, and the agency has set a target action date under the Prescription Drug User Fee Act (PDUFA) of April 27, 2013.

About Cobicistat

Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. Unlike ritonavir, cobicistat acts only as a pharmacoenhancing or “boosting” agent and has no antiviral activity. Gilead submitted an NDA to FDA for cobicistat on June 28, 2012, and a PDUFA date of April 28, 2013 has been set.

TAF, elvitegravir and cobicistat are investigational products and their safety and efficacy have not yet been established.

U.S. full prescribing information for Stribild is available at www.Stribild.com.

U.S. full prescribing information for Truvada is available at www.Truvada.com.