Gilead Sciences, Inc.Patrick O’Brien, 650-522-1936 (Investors)Cara Miller, 650-522-1616 (Media)
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 Stribild (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.
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/mm. 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 .
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.
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.
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.
Stribild contains four Gilead compounds in a complete once-daily, single tablet regimen: elvitegravir 150 mg; cobicistat 150 mg; emtricitabine 200 mg; and tenofovir disoproxil fumarate 300 mg. Stribild is indicated as a complete regimen for the treatment of HIV-1 infection in adults who are antiretroviral treatment-naïve. Stribild does not cure HIV-1 infection.
Do not use with drugs highly dependent on these factors for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events.
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including risks related to the possibility of unfavorable 48-week results from this or other clinical trials involving TAF, including the trial evaluating the single tablet regimen of TAF, darunavir, cobicistat and emtricitabine. Further, Gilead may be unable to obtain clinical trial results in the timelines currently anticipated and may need to modify or delay the clinical trials or to perform additional trials. Further, Gilead may make a strategic decision to discontinue development of TAF if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. There is also risk of failing to obtain approvals from regulatory authorities for TAF, alone or in combination with other products, and the New Drug Applications for elvitegravir and cobicistat may not be approved by the U.S. Food and Drug Administration or other regulatory agencies in the timelines anticipated or at all. As a result, these product candidates as standalone agents or as part of single tablet regimens may never be successfully commercialized. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2012, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.