Today the Food and Drug Administration (FDA) approved the HIV medication emtricitabine/tenofovir alafenamide (F/TAF, Descovy) as the second-ever drug for pre-exposure prophylaxis, PrEP, in the United States.
F/TAF is approved as PrEP for adults who are at risk for HIV, yet the FDA stopped short of recommending the new regimen "for receptive vaginal sex" (i.e., cisgender women and transgender men), noting in its approval notice that "the effectiveness in this population has not been evaluated."
The labeling decision is in line with an August recommendation from the FDA's expert panel, which voted 16 to 2 in favor of approving the drug for men and transgender women who have sex with men but 10 to 8 against its approval in cisgender women.
Gilead, the maker of F/TAF, was advocating for a broader PrEP label based on the experience of its existing PrEP regimen, emtricitabine/tenofovir disoproxil fumarate (F/TDF, Truvada), which is approved for nearly any patient considered at high risk for HIV infection. Yet it was rebuffed by the federal advisory panel.
Seven years ago, F/TDF (Truvada) became the first HIV medication to be approved to prevent HIV. F/TAF is essentially a new-and-improved version of F/TDF. One of its key ingredients -- the NRTI tenofovir alafenamide -- is thought to be safer than F/TDF's tenofovir disoproxil fumarate.
Yet when Gilead applied for FDA approval of F/TAF for PrEP, it submitted data from a large clinical trial called DISCOVER that included only men and transgender women who have sex with men.
"It's incredible that [Gilead] would do a very large study and not include women," said Catherine Chappell, M.D., M.Sc., assistant professor of obstetrics, gynecology, and reproductive sciences with the University of Pittsburgh.
DISCOVER found that F/TAF was non-inferior to F/TDF and led to better bone and renal outcomes, although researchers have subsequently raised concerns about weight gain possibly associated with TAF.
DISCOVER has also been criticized for not including enough people of color. To date, F/TAF's efficacy as PrEP has not been studied in cisgender women in a similar, large-scale trial.
"In this hot time when we are trying to include women in studies, you can't submit an abstract to a conference without submitting some sort of sex difference [data]," said Chappell. "And they completely did not include women."
One day after the approval was announced, the FDA issued a statement delcaring "Gilead Sciences has a post marketing commitment (PMC) to conduct a randomized, comparative trial to evaluate the safety and efficacy of Descovy for PrEP in cisgender women and adolescent girls weighing at least 35 kg, who are at risk of sexually acquired HIV-1 infection."
Activists and researchers have also raised the issue as to whether the improved safety data for F/TAF over F/TDF is enough to justify switching patients over who aren't having any adverse kidney or bone density events with F/TDF, especially when a generic (and hopefully cheaper) form of Truvada is soon to hit the U.S. market in 2021 and might bring down the price of accessing PrEP over brand-name Descovy.
Back in 2012, the FDA gave F/TDF a broad label based on clinical data from the iPrEx trial, which included men and transgender women who have sex with men, and from the Partners PrEP trial, which included heterosexual couples, including cisgender women.
F/TAF was approved in 2016 for HIV-positive people as part of a treatment regimen. As part of that approval package, the drug's safety has been evaluated in cisgender, HIV-positive women -- but its efficacy as an HIV prevention regimen has not.
F/TAF for PrEP is contraindicated in people who have hepatitis B, and it may only be initiated in people who have a confirmed HIV-negative test at least three months prior to use.