Gilead Submits Request for FDA Approval of Tenofovir Alafenamide Coformulation

Gilead Sciences this week announced that it has submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval of a single-tablet regimen containing tenofovir alafenamide (TAF) -- a new version of the widely used antiretroviral that causes less kidney and bone toxicity -- coformulated with its new integrase inhibitor elvitegravir, cobicistat, and emtricitabine.

Tenofovir disoproxil fumarate (Viread, also in the Truvada, Atripla, Complera, and Stribild coformulations) is among the most widely prescribed antiretroviral drugs. It is highly effective and generally regarded as safe and well-tolerated, but it can cause kidney toxicity in susceptible individuals and is associated with bone loss soon after starting treatment. TAF is a new formulation designed to produce higher levels of the active drug in HIV-infected cells, which allows for lower dosing and less drug exposure for the kidneys and bones.

In Phase 3 clinical trials the new single-tablet regimen worked as well as Stribild -- a similar coformulation containing TDF -- but with less effect on bone and kidney biomarkers. Gilead is also working on a single-tablet regimen containing TAF plus the protease inhibitor darunavir, cobicistat, and emtricitabine.

Below is an edited excerpt from a Gilead press release describing TAF and the FDA submission.

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Tenofovir Alafenamide (TAF)-Based Single Tablet Regimen for HIV

• High Rates of Viral Suppression and Improved Renal and Bone Safety Demonstrated in Phase 3 Studies

• First of Several TAF-Based Single Tablet Regimens Being Evaluated by Gilead

Foster City, CA -- November 6, 2014 --Gilead Sciences, Inc. (Nasdaq:GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide (TAF) 10 mg (E/C/F/TAF) for the treatment of HIV-1 infection in adults. The data submitted in the NDA support the use of the regimen among adult and adolescent treatment-naive HIV individuals, virologically suppressed patients who switch regimens, and those with renal impairment. If approved, E/C/F/TAF would be Gilead’s first single tablet regimen to contain TAF.

TAF is an investigational, novel prodrug of tenofovir, the active agent in Gilead’s Viread (tenofovir disoproxil fumarate). TAF is a more targeted form of tenofovir than Viread that has demonstrated high antiviral efficacy at a dose that is 10 times lower, as well as an improved renal and bone safety profile.

"This TAF-based regimen has the potential to provide a range of HIV patients with a highly effective and well-tolerated new treatment option with a favorable safety profile," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "Gilead remains focused on advancing next-generation therapies that have the potential to improve HIV treatment over the long-term and TAF will be the cornerstone of future Gilead single tablet regimens."

The NDA for E/C/F/TAF is supported by 48-week data from two pivotal Phase 3 studies (Studies 104 and 111) in which the regimen met its primary objective of non-inferiority compared to Gilead’s Stribild (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among treatment-naive patients. In the studies, E/C/F/TAF demonstrated improved renal and bone safety compared to Stribild. The NDA is also supported by data from additional Phase 3 studies evaluating the TAF-based regimen among virologically suppressed patients who switched to E/C/F/TAF and among patients with renal impairment. In addition, the filing is supported by Chemistry, Manufacturing and Controls (CMC) information on the individual components and the co-formulated single tablet regimen.

Gilead plans to submit a regulatory application for E/C/F/TAF in the European Union by the end of 2014.

TAF and TAF-based regimens are investigational products and have not been determined safe or efficacious.

About Gilead Sciences

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 and South America, Europe and Asia Pacific.

U.S. full prescribing information for Stribild and Viread, including BOXED WARNING for both products, is available at www.gilead.com.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5

11/6/14

Source

Gilead Sciences. Gilead Submits New Drug Application to U.S. Food and Drug Administration for Tenofovir Alafenamide (TAF)-Based Single Tablet Regimen for HIV. Press release. November 6, 2014.