Efforts to combine tenofovir, emtricitabine (FTC) and efavirenz in one pill are still failing to produce a product that is bioequivalent to dosing the three drugs separately, Gilead Sciences announced yesterday.
Gilead began attempts to coformulate the drugs in December 2004 when it announced a joint partnership with Bristol Myers Squibb, the United States' manafacturer of efavirenz (Sustiva) to investigate creating a three-drugs-in-one-tablet combination. Gilead has already received marketing approval for Truvada, a combination tablet of tenofovir and emtricitabine, and the use of these two drugs in combination with efavirenz is recommended by the United States Department of Health and Human Services' antiretroviral treatment guidelines as one of the preferred combinations for first-line treatment.
Gilead says it is proceeding with the evaluation of up to three new formulations, developed based on bi-layer technology. This bi-layer technology involves co-formulation of Truvada and Sustiva as individually formulated layers, combined together in one tablet. Gilead will initiate the bioequivalence studies in humans and stability studies of the new formulations over the next several months.
Pending the results of the planned bioequivalence studies, Gilead and Bristol-Myers Squibb anticipate filing a New Drug Application with the US Food and Drug Administration in the first half of 2006.
A once-daily fixed dose combination of the three drugs will also be of interest for use in resource-limited settings, but the registration and marketing of such a product is complicated by the fact that the marketing rights to efavirenz outside the United States and five western European countries are owned by Merck, who market efavirenz as Stocrin. Merck has issued a voluntary license to the South African pharmaceutical manufacturer Thembalami to make efavirenz for the southern African market too. Gilead announced a similar arrangement on tenofovir and Truvada manufacture and distribution in Africa with Aspen Pharmacare in April 2005.