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New Single-Tablet HIV Treatment Submitted for FDA Review

Once-daily regimen consists of emtricitabine, tenofovir, and rilpivirine

Gilead Sciences has submitted a new drug application (NDA) to the FDA for an investigational, once-daily, single-tablet regimen that combines the company’s emtricitabine and tenofovir alafenamide (TAF) with rilpivirine (Edurant; Janssen Sciences Ireland) (R/F/TAF) for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adult and pediatric patients 12 years of age and older. The data submitted in the NDA support the use of R/F/TAF in patients who are HIV treatment-naïve or who are virologically suppressed and want to replace their current antiretroviral treatment regimen.

A “priority review” voucher acquired in November 2014 was submitted to the FDA along with the R/F/TAF NDA. Under the Prescription Drug User Fee Act (PDUFA), the anticipated target action date for the R/F/TAF NDA is 6 months after the FDA’s acceptance of the filing.

TAF is an investigational 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 compared with TDF in clinical trials in combination with other antiretroviral agents.

In addition to R/F/TAF, two other TAF-based HIV treatments are under FDA review. In November 2014, Gilead filed an NDA for an investigational, once-daily, single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF (E/C/F/TAF). Gilead filed another NDA in April 2015 for two doses of an investigational, fixed-dose combination of emtricitabine and tenofovir alafenamide (F/TAF) for use in combination with other HIV antiretroviral agents. Under the PDUFA, the FDA has set a target action date of November 5, 2015, for E/C/F/TAF and April 7, 2016, for F/TAF.

The current NDA is supported by a bioequivalence study demonstrating that R/F/TAF achieved the same drug levels of emtricitabine and TAF in the blood as E/C/F/TAF (10-mg TAF dosage) and the same drug levels of rilpivirine as a 25-mg dose of rilpivirine alone. The safety and efficacy of TAF are supported by clinical studies in patients with HIV, including treatment-naïve adults and adolescents; virologically suppressed adults who switched regimens; and adults with mild-to-moderate renal impairment. In clinical trials, TAF-based treatment (administered as E/C/F/TAF) resulted in noninferior efficacy and improved renal and bone laboratory parameters compared with TDF-based therapy (administered as E/C/F/TDF or Stribild [Gilead Sciences]).

A fourth investigational TAF-based regimen containing Gilead’s TAF, emtricitabine, and cobicistat, and Janssen’s darunavir (Prezista; D/C/F/TAF) is also being developed. Under an agreement, Gilead is transferring to Janssen further development of the regimen and, subject to regulatory approval, the manufacturing, distribution, and commercialization of the product worldwide.

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

Source: Gilead Sciences; July 1, 2015.

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