As proof that even experienced biotechs can hit unexpected regulatory roadblocks, Gilead Sciences Inc. received a stunning refuse-to-file (RTF) letter for its new drug application (NDA) seeking approval of HIV single-tablet regimen Truvada (emtricitabine/tenofovir disoproxil fumarate) plus Tibotec Pharmaceuticals Ltd.'s TMC278 (rilpivirine).

The news, along with Gilead's fourth quarter and 2010 earnings, came after markets closed Tuesday. The company's shares (NASDAG:GILD) closed at $38.16, down 15 cents.

Foster City, Calif.-based Gilead submitted the application in November 2010. The Tibotec-partnered program – nicknamed Btripla – is intended to be a safer follow-up to Atripla, a single-pill combination of Truvada plus Bristol-Myers Squibb Co.'s Sustiva (efavirenz) that pulled in $2.93 billion in sales in 2010.

The NDA was based on a bioequivalence study showing that the Btripla formulation achieved the same levels of medication in the blood as the individual component products dosed simultaneously. (See BioWorld Today, Nov. 24, 2010.)

In the RTF, the FDA requested additional chemistry, manufacturing and controls information, stating that the NDA "does not contain sufficient information on the analytical methodology to establish acceptable levels of recently identified degradants related to emtricitabine."

Gilead execs said they are working on resolving those issues and anticipate resubmitting the application by the end of the first quarter.

Meanwhile, a separate NDA for TMC278 remains under review. Tibotec, a unit of New Brunswick, N.J.-based Johnson & Johnson, filed for regulatory approval of the non-nucleoside reverse transcriptase inhibitor for treatment-naïve HIV-1-infected adults in July.

Gilead and Tibotec have been collaborating on the single-pill combination since mid-2009. Under terms of that deal, Gilead is taking the lead on the manufacturing, distribution and commercialization of the drug worldwide, excluding the developing world and Japan. (See BioWorld Today, July 20, 2009.)