Complera, (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) a complete single-tablet regimen for the treatment of HIV-1 infection in treatment-naive adults (adults never treated before), has been approved by the U.S. Food and Drug Administration (FDA). Complera blends three antiretroviral medications in a single daily tablet – Gilead’s Truvada®, 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 (labeled as Edurant in the United States by Janssen Therapeutics, Division of Janssen Products, LP).

In August 2004 and May 2011 the FDA approved Truvada and rilpivirine, respectively, for use as part of HIV combination therapy.

Tony Mills, MD, Director of Medical Research, Anthony Mills MD, Inc. and a participating investigator in ongoing Complera studies explained:

“In the 30 years since the first AIDS cases were reported, we’ve made incredible strides in the treatment of this disease. 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.”

Complera’s approval is backed by 48-week information from two Phase 3 double-blind, active controlled, randomized investigations (ECHO and THRIVE) led by Tibotec that assessed the safety and effectiveness of rilpivirine in comparison to efavirenz among HIV-1 adults who had never been treated before.

Both study groups were administered with a background regimen, in the rilpivirine group the majority of patients received Truvada. Led by Gilead, a bioequivalence investigation showed that the co-formulated single-tablet treatment achieved the equivalent levels of medication in the blood as emtricitabine plus tenofovir disproxil fumarate.

John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences said:

“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. Tremendous progress has been made in the field of HIV, but we recognize new therapies are still needed, and we contoptions that address the needs of patients.”

For HIV-1 patients who have never been treated before (treatment-naïve patients), Complera is the second complete antiretroviral treatment regimen for HIV-1 available in a once-daily single pill. The first, Atripla® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg), is labeled by Gilead and Bristol-Myers Squibb. HIV-1 infection is not cured by Complera nor does it help prevent the transmission of HIV to other individuals. Boxed Warnings for Complera including, lactic acidosis/severe hepatomegaly with steatosis and post treatment acute exacerbation of hepatitis B; see below for further important safety information. The following points should be taken into consideration when starting therapy with Complera:

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

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

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

Written by Grace Rattue Source: Gilead