Gilead Submits New Drug Application to U.S. Food and Drug Administration for Single Tablet Regimen for HIV Containing Rilpivirine, Emtricitabine and Tenofovir Alafenamide

Gilead Sciences, Inc.

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 that combines Gilead's emtricitabine 200 mg and tenofovir alafenamide (TAF) 25 mg with rilpivirine 25 mg (R/F/TAF) from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, for the treatment of 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 among 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 from Knight Therapeutics 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 six months after the FDA's acceptance of the filing. "R/F/TAF is Gilead's third TAF-based filing in less than a year, and we are looking forward to the potential to offer people living with HIV another effective treatment option with a favorable safety profile," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "The R/F/TAF filing also represents Gilead's next collaboration with Janssen in our combined efforts to increase and potentially improve HIV treatments for a range of patients." TAF is a novel, 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 as compared to TDF in clinical trials in combination with other antiretroviral agents. In addition to R/F/TAF, two other TAF-based HIV treatments are also under FDA 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). Gilead filed another NDA in April 2015 for two doses of an investigational, fixed-dose combination of emtricitabine and tenofovir alafenamide (200/10 mg and 200/25 mg) (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. Marketing Authorization Applications in the European Union were fully validated on December 23, 2014, and May 28, 2015, for E/C/F/TAF and F/TAF respectively. Gilead plans to submit a regulatory application for R/F/TAF in the European Union in the third quarter of 2015. 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 (Edurant®) alone. The safety and efficacy of TAF is supported by a number of clinical studies in a range of patients with HIV, including treatment-naïve adults and adolescents, virologically suppressed adults who switched regimens and adults with mild-to-moderate renal impairment. In studies, TAF-based treatment (administered as E/C/F/TAF) resulted in non-inferior efficacy and improved renal and bone laboratory parameters as compared to TDF-based therapy (administered as E/C/F/TDF or Stribild®). The R/F/TAF filing is the latest step in an expanded development and commercialization agreement between Gilead and Janssen, first established in 2009. Under this agreement, and pending the product's approval, Gilead will be responsible for the manufacturing, registration, distribution and commercialization of the regimen in most countries, while Janssen will distribute it in approximately 17 markets and have co-detailing rights in several key markets, including the United States. The original agreement was established for the development and commercialization of Complera®, marketed as Eviplera® in the European Union. A fourth investigational TAF-based regimen containing Gilead's TAF, emtricitabine and cobicistat, and Janssen's darunavir (D/C/F/TAF) also is under development under another licensing agreement. Under the agreement, Gilead is transferring to Janssen further development of the regimen and, subject to regulatory approval, the manufacturing, registration, distribution and commercialization of the product worldwide. TAF-based regimens are investigational products and have not been determined to be safe or efficacious.