FDA approves single-tablet regimen for HIV-1 infection in treatment-naïve adults

FDA has approved emtricitabine/rilpivirine/tenofovir disoproxil fumarate (Complera, Gilead Sciences), a complete single-tablet regimen for the treatment of HIV-1 infection in treatment-naïve adults.

Complera combines 3 antiretroviral medications in 1 daily tablet - Gilead's Truvada, which is a fixed-dose combination of the 2 nucleoside reverse transcriptase inhibitors emtricitabine and tenofovir disoproxil fumarate, and Tibotec Pharmaceuticals’ non-nucleoside reverse transcriptase inhibitor, rilpivirine (Edurant, Janssen Therapeutics, Division of Janssen Products). Truvada and rilpivirine were approved by FDA in August 2004 and May 2011, respectively, for use as part of HIV combination therapy.

“HIV therapy has emerged as a multi-drug cocktail during the last decade,” Randy Vogenberg, PhD, told Drug Topics. Vogenberg is principal at the Institute for Integrated Healthcare in Sharon, Mass., and executive director of the Biologic Access & Finance program at The Jefferson School of Population Health in Philadelphia.

“Joining other 2- and 3-drug combination products . . . is the continuing trend that aids adherence, which is crucial to successful chronic care management of HIV,” Vogenberg said.

"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," said Tony Mills, MD, director of medical research, Anthony Mills MD, Inc., and a participating investigator in ongoing Complera studies, in a company press release.

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 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, and was approved by FDA in July 2006.

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. The following points should be considered when initiating therapy with Complera:

• More rilpivirine-treated subjects with HIV-1 RNA >100,000 copies/mL at the start of therapy experienced virologic failure compared to subjects with HIV-1 RNA 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