Gilead Sciences has submitted a supplemental new drug application requesting Food and Drug Administration (FDA) approval of its Descovy combination pill for pre-exposure prophylaxis (PrEP), according to a company press release. Descovy contains tenofovir alafenamide (TAF)—an updated formulation of tenofovir that is easier on the kidneys and bones—and emtricitabine.

As previously reported, researchers presented data last month at the 2019 Conference on Retroviruses and Opportunistic Infections (CROI) showing that Descovy works as well as the widely used Truvada pill containing tenofovir disoproxil fumarate (TDF) and emtricitabine, currently the only FDA-approved PrEP regimen.

The Phase III DISCOVER trial enrolled more than 5,300 mostly gay and bisexual men and a small number of transgender women considered at high risk for HIV. Participants were randomly assigned to take Descovy or Truvada once daily for 96 weeks. (On-demand or intermittent dosing before and after sex—dubbed PrEP 2-1-1—was not evaluated in this study.)

During follow-up, there were seven new infections in the Descovy group and 15 in the Truvada group, giving incidence rates of 0.16 and 0.34 per 100 person years. This means that if 100 people were followed for a year, less than one new infection would be expected using either PrEP pill. Among those who became HIV positive, five were suspected of having already had undetected infection at study entry and 15 were found to have low tenofovir levels in dried blood spots, a method used to measure adherence.

Given the small number of infections in both groups, the study did not have the statistical power to show whether Descovy works better than Truvada—but it showed that it is noninferior, or at least as good.

Descovy and Truvada were both generally safe and well tolerated. Side effects were usually mild or moderate, and only 1 percent of Descovy recipients and 2 percent of Truvada recipients stopped treatment because of adverse events.

Markers of kidney safety were more favorable in the Descovy group compared with the Truvada group. Two people taking Descovy and six people taking Truvada stopped PrEP because of kidney problems. Bone mineral density at the spine and hip rose slightly in the Descovy arm while declining a bit in the Truvada arm.

While these differences were statistically significant—meaning they probably aren’t attributable to chance alone—it’s not clear whether they predict clinical outcomes such as kidney failure or bone fractures. Brad Hare, MD, of Kaiser Permanente San Francisco, who presented the study findings at CROI, suggested that Descovy may be a better PrEP alternative for people at risk for kidney problems.

Gilead used a priority review voucher for the application, which speeds up FDA review. The anticipated review time is six months, so Descovy could be approved for PrEP this fall.

Click here to read the Gilead’s press release.

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