Gilead Submits Applications for FDA Approval of Elvitegravir and Cobicistat


On June 27 Gilead Sciences announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for marketing approval of its new integrase inhibitor, elvitegravir, for use in combination antiretroviral therapy for treatment-experienced adults with HIV. The following day the company also requested approval of its novel boosting agent cobicistat.

[Editor's note: this report has been updated to add approval request for cobicistat on June 28, 2012]

Integrase inhibitors work by preventing HIV from inserting its genetic material into a host cell's chromosomes, a necessary step in viral replication. Integrase inhibitors are among the most well-tolerated antiretrovirals, perhaps because they do not interfere with essential host cell functions.

If approved, elvitegravir is likely to be the second integrase inhibitor to enter the market, after Merck's raltegravir (Isentress). Phase 3 studies have shown that elvitegravir matches raltegravir in safety and efficacy when used in combination regimens. ViiV Healthcare and Shionogi are also working on a promising integrase inhibitor, dolutegravir, which has been shown to work as well as the NNRTI efavirenzand raltegravir.

The day after the elvitegravir request, Gilead also submitted an NDA for its novel pharmacoenhancing agent cobicistat. Like most HIV protease inhibitors, elvitegravir requires pharmacokinetic boosting to reach optimal levels in the body. Cobicistat works as well as ritonavir (Norvir) as a booster for atazanavir (Reyataz), but unlike ritonavir it does not have anti-HIV activity of its own.

Elvitegravir and cobicistat have taken an unusual regulatory path. Typically individual drugs are evaluated and approved first, and are then eligible to be included in coformulations. In contrast, Gilead first sought approval of a 4-in-1 combination pill known as the Quad, which contains elvitegravir, cobicistat, and tenofovir/emtricitabine (the NRTI duo in Truvada). The FDA's Antiviral Drugs Advisory Committee recommended approval of the Quad for treatment-naive patients in May, with a final agency decision expected by late summer.

The separate elvitegravir application filed this week is for previously treated patients. Gilead indicated that it is working with Janssen and Bristol-Myers Squibb, respectively, to develop coformulations containing cobicistat with darunavir (Prezista) and with atazanavir.



Gilead Sciences. Gilead Submits New Drug Application to U.S. FDA for HIV Integrase Inhibitor Elvitegravir for Treatment-Experienced Patients. Press release. June 27, 2012.

Gilead Sciences. Gilead Submits New Drug Application to U.S. FDA for Boosting Agent Cobicistat. Press release. June 28, 2012.