FDA approves Descovy for treatment of HIV

The FDA has approved Descovy, a fixed-dose combination tablet containing emtricitabine and tenofovir alafenamide, for the treatment of HIV, according to the drug’s manufacturer.

Descovy (emtricitabine/tenofovir alafenamide [F/TAF]; Gilead Sciences) is administered as a single oral tablet taken daily in combination with other antiretroviral agents. The formulation includes 200 mg emtricitabine and 25 mg tenofovir alafenamide, and it is indicated for adults and pediatric patients aged 12 years and older without hepatitis B virus infection and with creatinine clearance of at least 30 mL/min.

Norbert Bischofberger

F/TAF regimens noninferior to F/TDF regimens

“As part of a single tablet regimen or partnered with a third agent, the components of Descovy offer patients a simple and effective combination with a safety profile that has the potential to improve health,” Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, said in a press release. “With today’s approval, Gilead is now able to offer patients and providers in the United States a range of options from our TAF-based portfolio, which is designed to help address the diverse needs of HIV patients worldwide.”

According to the release, the approval is supported by several phase 3 studies demonstrating noninferiority of the F/TAF-based regimen Genvoya (elvitegravir/cobicistat/F/TAF [E/C/F/TAF]; Gilead Sciences) compared with Stribild (E/C/F/tenofovir disoproxil fumarate [E/C/F/TDF]; Gilead Sciences), as well as other F/TDF-based regimens, when administered to HIV patients virally suppressed by F/TDF-based regimens or to patients with no exposure to ART. Tests of renal and bone safety parameters also showed TAF to be favorable over Viread (TDF; Gilead Sciences) and efficacious when administered at a dose less than one-tenth that of TDF.

The most common adverse reaction to F/TAF was nausea, according to the release. Drug warnings and precautions include fat redistribution; immune reconstitution syndrome; new onset or worsening renal impairment; and bone loss and mineralization defects.

Patients maintain viral suppression when switching from F/TDF to F/TAF

Recent data published in The Lancet HIV by Joel E. Gallant, MD, MPH, medical director of specialty services at Southwest CARE Center in Santa Fe, New Mexico, and colleagues also suggests a switch from F/TDF-containing regimens to F/TAF-containing regimens would have no negative impact on viral suppression and patient safety.

Joel E. Gallant

In the randomized, double blind trial, the researchers enrolled virally suppressed adult HIV patients receiving F/TDF-based regimens from 78 North American and European sites. Eligible participants were required to have received their previous regimen for at least 6 months and demonstrate an estimated glomerular filtration rate (eGFR) of more than 50 mL/min. Researchers randomly assigned patients to either continue their current treatment (n = 330) or switch the tenofovir component of the regimen to F/TAF (n = 333), with those switching assigned either 10 mg TAF or 25 mg TAF depending on the third agent of their regimen. Post-baseline study visits were conducted until week 96. The primary study outcome was the proportion of patients with plasma HIV-1 RNA less than 50 copies/mL at week 48, with secondary and safety outcomes including changes in hip and spine bone mineral density, serum creatinine and CD4 cell count.

Approximately 94% of patients in the F/TAF group maintained viral suppression through week 48, which was similar to the 93% rate observed among the F/TDF group (adjusted difference = 1.3%; 95% CI, –2.5 to 5.1). Results among patient subgroups were similar, and both regimens were well-tolerated. Although there were no discontinuations due to renal adverse events and few fractures, exploratory analyses of eGFR, urine protein-to-creatinine ratio, and hip and spine BMD consistently favored the F/TAF group.

“A switch from regimens containing fixed-dose combination [F/TDF] to fixed-dose combination [F/TAF] was associated with maintenance of virological suppression with noninferior virological efficacy and overall tolerability, along with improvement in markers of renal and bone toxicity,” Gallant and colleagues wrote. “The combination containing [TAF] has the potential to be an important [nucleoside reverse-transcriptase inhibitors (NRTI)] backbone in the treatment of patients with HIV, with safety advantages over that containing [TDF].”

Encouraging findings prompt new questions

In a related editorial, Mark A. Boyd, MD, FRACP, and David A. Cooper, MD, DSc, FRACP, both of the Kirby Institute for Infection and Immunity in Society, University of New South Wales, Australia, wrote that the renal and BMD advantages observed with TAF are a “major advance” in providing safe HIV treatment. However, more research will be needed to answer remaining questions concerning the NRTI, such as the treatment’s susceptibility to negative drug interactions or its potential for use as pre-exposure prophylaxis, or PrEP.

“The understanding of the public health benefits of treatment as prevention and as PrEP in high risk HIV-negative people has added a new dimension to our assessment of their use,” they wrote. “Although [TAF] seems likely to make [ART] safer, questions remain about its benefit for both the general population and most people living with HIV in countries with a high prevalence of tuberculosis.” – by Dave Muoio

References:

Gallant JE, et al. Lancet HIV. 2016;doi:10.1016/S2352-3018(16)00024-2.

Boyd MA, et al. Lancet HIV. 2016;doi:10.1016/S2352-3018(16)00039-4.

Disclosures: Bischofberger is a paid employee of Gilead Sciences. Gallant reports research support from Bristol-Myers Squibb, CytoDyn, Gilead Sciences, Merck, Sangamo BioSciences, Vertex Pharmaceuticals and ViiV Healthcare, as well as consulting fees from Bristol-Myers Squibb, Gilead Sciences, Merck and Janssen Therapeutics. Please see the full study and commentary for a list of all other authors’ relevant financial disclosures.