The U.S. Food and Drug Administration (FDA) has approved the single-tablet HIV treatment regimen Odefsey (emtricitabine/rilpivirine/tenofovir alafenamide), which includes a new, safer version of tenofovir. Pronounced “oh-DEF-see,” the tablet is an updated version of Complera (rilpivirine/tenofovir disoproxil fumarate/emtricitabine), swapping tenofovir alafenamide, or TAF, for tenofovir disoproxil fumarate, or TDF.
Research has shown that TAF is safer to the bones and kidneys than TDF and suppresses HIV just as well. TAF more efficiently enters cells, requiring a dose one tenth that of TDF, and leads to 90 percent less drug in the bloodstream where it may cause toxicities.
The smallest single-tablet antiretroviral (ARV) regimen on the market to date, Odefsey is the second such tablet to include TAF. Gilead Sciences’ Genvoya (elvitegravir/cobicistat/emtricitabine/TAF), an updated, TAF-inclusive version of Stribild (elvitegravir/cobicistat/emtricitabine/TDF), was approved in November 2015. Gilead is expecting word from the FDA in April 2016 about its application for approval of a TAF-inclusive version of Truvada (TDF/emtricitabine). (The new Truvada will not be approved as pre-exposure prophylaxis (PrEP) against HIV, and recent research has questioned whether TAF will work as well as TDF as prevention.)
Gilead manufactures tenofovir and emtricitabine, while Janssen owns the rilpivirine (brand name Edurant) component of Odefsey.
Odefsey is approved for HIV-positive individuals 12 years of age and older who have never been treated for the virus before and have a viral load no greater than 100,000. The tablet is also approved as a replacement for a stable antiretroviral (ARV) regimen. People who fall into this category include those who have had a fully suppressed viral load for at least six months and have never experienced treatment failure on ARVs, and who have never had to swap HIV medications because of resistance to any of the three drugs included in Odefsey.
There is a boxed warning for Odefsey, cautioning about the risks of lactic acidosis (when lactic acids build up in the bloodstream) and severe hepatomegaly with steatosis (liver enlargement from fat), as well as post-treatment exacerbation of hepatitis B virus (HBV).
The approval is based on a study showing that Odefsey led to similar drug levels of emtricitabine and TAF in the blood as Genvoya, as well as similar drug levels of rilpivirine as when rilpivirine is given on its own. The safety, efficacy and tolerability of Odefsey have been established in clinical trials of rilpivirine-based treatment and emtricitabine/TAF-based treatment (given as Genvoya) among a range of people with HIV. These study participants included adults and adolescents who had not been treated before, adults who were already virally suppressed on a regimen based on protease inhibitors, non-nucleoside reverse transcriptase inhibitors, or integrase strand transfer inhibitors, as well as adults with viral suppression and mild-to-moderate kidney impairment.
For a Gilead press release on the approval, click here.
For the full prescribing information, including the boxed warning, click here.