Agency requires additional CMC information for Truvada and TMC278 combo.

Gilead Sciences received a refuse to file notification from the FDA regarding its NDA for the single-tablet regimen of Truvada® and TMC278. The agency requested additional information with respect to chemistry, manufacturing, and controls.

TMC278 (rilpivirine hydrochloride) is Tibotec Pharmaceuticals’ investigational non-nucleoside reverse transcriptase inhibitor. Truvada is a nucleoside reverse transcriptase inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Truvada combines emtricitabine, marketed on its own as Emtriva, and tenofovir disoproxil fumarate, which is sold as Viread. Emtriva and Viread are both marketed by Gilead.

FDA’s letter stated that the application did not contain sufficient data on the analytical methodology used to establish acceptable levels of recently identified degradants related to emtricitabine. “We expect to be in a position to resubmit the Truvada/TMC278 NDA with the additional requested information prior to the end of the first quarter of this year,” says Norbert Bischofberger, Ph.D., evp of R&D and CSO, Gilead Sciences.

Sales of Truvada increased to $681.7 million for the fourth quarter of 2010 from $670.7 million in the fourth quarter of 2009. For 2010, Truvada sales increased 6% to $2.65 billion from $2.49 billion in 2009. Gilead attributes the boost to sales growth in the U.S. and Europe. Viread sales also grew in the U.S., Europe, and Latin America during 2010, contributing to the 9.6% increase from $667.5 million in 2009 to $732.2 million. Gilead does not report numbers specifically for Emtriva.

Gilead’s HIV portfolio is rounded out by Atripla, which currently is the only complete antiretroviral regimen with single-tablet, once-daily dosing. It combines efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. Atripla made $2.93 billion in 2010 sales, a 23% spike from 2009.

The Truvada/TMC278 combination is also being developed as a once-daily treatment. Gilead licensed TMC278 from Tibotec in July 2009. Gilead is leading the manufacture, registration, distribution, and commercialization worldwide excluding Japan and the developing world. Tibotec has the right to co-promote in Gilead’s regions and remains responsible for the commercialization of TMC278 as a standalone product.

Patient recruitment for a Phase III program was completed in early 2009, according to Tibotec. The two double-blind studies include HIV-1 infected individuals who have not previously received antiretroviral treatment. The trials compare 25 mg once-daily TMC278 against 600 mg once-daily efavirenz in combination with two NRTIs.

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