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Gilead Requests Approval of Tenofovir Alafenamide Dual Combination Pill

Gilead Sciences has requested U.S. Food and Drug Administration approval of a combination pill containing emtricitabine plus tenofovir alafenamide (TAF), a new formulation that is easier on the kidneys and bones, according to a company press release. If approved, the new coformulation could take the place of Truvada for HIV treatment, though its effectiveness for pre-exposure prophylaxis, or PrEP, is not yet known.

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Tenofovir disoproxil fumarate or TDF (Viread, also in Truvada, Atripla, and other Gilead single-tablet regimens) is one of the most widely used antiretroviral drugs. TAF is a pro-drug that delivers the active agent to HIV-infected cells more efficiently than TDF. TAF produces adequate intracellular drug levels with lower doses, which means lower concentrations in the blood plasma and less drug exposure for organs and tissues.

As reported at the recent 2015 Conference on Retroviruses and Opportunistic infections, Phase 3 studies have shownthat a single-tablet regimen containing TAF, emtricitabine, elvitegravir, and cobicistat was equally effective at suppressing HIV but hadless detrimental effects on the kidneys and bones than the existing Stribild coformulation containing TDF.

Below is an edited excerpt from a Gilead press release describing the TAF/emtricitabine new drug application. The company has also requested approval of the 4-drug single-tablet regimen described above, and stand-alone TAF is being developed as a treatment for hepatitis B.

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-dose Combination of Emtricitabine/Tenofovir Alafenamide for HIV Treatment

Potential New Backbone for Future HIV Therapy Combinations

Foster City, Calif. -- April 7, 2015 -- 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 two doses of an investigational fixed-dose combination of emtricitabine and tenofovir alafenamide (200/10 mg and 200/25 mg) (F/TAF) for the treatment of HIV-1 infection in adults and pediatric patients age 12 years and older, in combination with other HIV antiretroviral agents.

TAF is a novel nucleotide reverse transcriptase inhibitor(NRTI) that has demonstrated high antiviral efficacy at a dose less than one-tenth that of Gilead’s Viread (tenofovir disoproxil fumarate, TDF), as well as improved renal and bone laboratory parameters as compared to TDF in clinical trials.

"Gilead has a long history of innovating HIV treatments, and with F/TAF we have the potential to further optimize therapies for HIV patients who face a lifetime of antiretroviral treatment," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "With its high antiviral efficacy and favorable safety profile, F/TAF may offer an improved backbone for a new generation of HIV regimens."

Today’s filing is Gilead’s second F/TAF-based NDA submitted to the FDA for review.  In November 2014, Gilead filed an NDA for an investigational once-daily single tablet regimen containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and TAF 10 mg (E/C/F/TAF). Under the Prescription Drug User Fee Act, the FDA has set a target action date of November 5, 2015. Additionally, a Marketing Authorization Application in the European Union for E/C/F/TAF was fully validated on December 23, 2014.

The F/TAF NDA is supported by data from Phase 3 clinical studies evaluating the safety and efficacy of E/C/F/TAF for the treatment of HIV-1 infection among treatment-naive adults, in which the F/TAF-based regimen (administered as E/C/F/TAF) resulted in non-inferior efficacy and improved renal and bone laboratory parameters as compared to F/TDF-based therapy (administered as E/C/F/TDF or Stribild).The NDA is also supported by data from additional Phase 3 studies evaluating the F/TAF-based regimen (administered as E/C/F/TAF) among treatment-naive adolescents, virologically suppressed adults who switched regimens, and adults with mild-to-moderate renal impairment. Lastly,bioequivalence studies demonstrated that the formulation of the fixed-dose combinations of F/TAF achieved the samedruglevelsin the blood as in E/C/F/TAF.

The recommended dose of F/TAF is 200/25 mg; if it is used in combination with a protease inhibitor that is administered with either ritonavir or cobicistat, the recommended dose is 200/10 mg.

Additional F/TAF-based regimens for HIV treatment are currently in development. In December 2014, Gilead announced the expansion of its existing agreements with Janssen Sciences Ireland UC for the development and commercialization of two new investigational once-daily single tablet regimens containing F/TAF. One combines F/TAF with Janssen’s rilpivirine. The other regimen contains F/TAF, cobicistat and Janssen’s darunavir.

Gilead plans to submit a regulatory application for F/TAF in the European Union in the second quarter of 2015.

F/TAF-based regimens are investigational products and have not been determined to be 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. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

4/8/15

Source

Gilead Sciences. Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-dose Combination of Emtricitabine/Tenofovir Alafenamide for HIV Treatment. Press release. April 7, 2014.

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