FDA approves Gilead's Complera for treatment of HIV-1 infection

Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Complera™ (emtricitabine/rilpivirine/tenofovir disoproxil fumarate), a complete single-tablet regimen for the treatment of HIV-1 infection in treatment-naïve adults. Complera combines three antiretroviral medications in one daily tablet - Gilead's Truvada^®, which is a fixed-dose combination of the two nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir disoproxil fumarate, and Tibotec Pharmaceuticals' non-nucleoside reverse transcriptase inhibitor, rilpivirine (marketed as Edurant™ in the United States by Janssen Therapeutics, Division of Janssen Products, LP). Truvada and rilpivirine were approved by the FDA in August 2004 and May 2011, respectively, for use as part of HIV combination therapy.

"In the 30 years since the first AIDS cases were reported, we've made incredible strides in the treatment of this disease," said Tony Mills, MD, Director of Medical Research, Anthony Mills MD, Inc. and a participating investigator in ongoing Complera studies. "The concept of a single-tablet regimen has become a goal in HIV drug development, and the standard of care in medical practice in the United States. However, no one therapy is appropriate for all patients. Given its efficacy, safety and convenience, the availability of Complera represents an exciting milestone in addressing the individual needs of patients new to HIV therapy."

The approval of Complera is supported by 48-week data from two Phase 3 double-blind, active controlled, randomized studies (ECHO and THRIVE) conducted by Tibotec that evaluated the safety and efficacy of rilpivirine compared to efavirenz among treatment-naïve HIV-1 infected adults. Both arms of the study were administered with a background regimen, in which the majority of patients in the rilpivirine arm received Truvada. A bioequivalence study, conducted by Gilead, demonstrated that the co-formulated single-tablet regimen achieved the same levels of medication in the blood as emtricitabine plus rilpivirine plus tenofovir disoproxil fumarate.

"Complera is the second complete single-tablet regimen that Gilead has introduced, and it represents a collaboration between two organizations that share a vision of simplifying HIV therapy for patients," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "Tremendous progress has been made in the field of HIV, but we recognize new therapies are still needed, and we continue to work to advance options that address the needs of patients."

Complera is the second complete antiretroviral treatment regimen for HIV-1 available to treatment-naïve patients in a single once-daily pill. The first, Atripla^® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), is marketed by Gilead and Bristol-Myers Squibb. Complera does not cure HIV-1 infection or help prevent the transmission of HIV to others. Complera has Boxed Warnings including lactic acidosis/severe hepatomegaly with steatosis and post treatment acute exacerbation of hepatitis B; see below for additional important safety information. The following points should be considered when initiating therapy with Complera:

• More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure compared to subjects with HIV-1 RNA less than 100,000 copies/mL at the start of therapy.
• The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz.
• More subjects treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz.
• Complera is not recommended for patients less than 18 years of age.

Gilead first entered into a license and collaboration agreement with Tibotec for the development and commercialization of Complera in July 2009. Under the terms of the agreement, Gilead will assume the lead role in the manufacturing, registration, distribution and commercialization of Complera in the United States, Canada, Brazil, the European Union, Australia and New Zealand. Tibotec will be responsible for the commercialization of rilpivirine as a stand-alone product and will hold rights to co-detail Complera in these territories. A marketing application for the emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen is currently pending in the European Union.

The companies also have finalized an agreement for the development and commercialization of the single-tablet regimen for the rest of world, including the developing world. Gilead will be responsible for the registration, distribution and commercialization of the single-tablet regimen in certain European countries, Latin America and the Caribbean. Tibotec will be responsible for all countries outside of the Gilead territories, the most significant of which include Asia Pacific, including Japan, the Middle East, Eastern Europe and all of Africa.