When FDA's Antiviral Advisory Committee finally voted last night whether to recommend an HIV prevention indication for Truvada (see previous posts), it turned out that some of the suspense was unwarranted: for men who have sex with men and HIV negative people in serodiscordant relationships (i.e., their stable partner is HIV positive), the group voted 19-3 and 19-2, respectively, to recommend approval.
The vote on "Question 1(c)," however (the panel voted on each proposed indication one at a time), was much closer. The question was whether to recommend approval for indication in "Other individuals at risk for acquiring HIV through sexual activity." As a committee member noted before the vote, this question was primarily about heterosexual women, many of whom face a high risk of HIV acquisition in the U.S. (not to mention globally), but in whom the clinical trials data have been less conclusive. It has been widely noted that the FEM-PrEP trial, testing Truvada in heterosexual women, was stopped when an interim review showed that it would not demonstrate efficacy. It has emerged subsequently, however, that adherence in FEM-PrEP was too low for the trial to have demonstrated an effect, regardless of the pill's actual efficacy. Women have been included in other studies of oral tenofovir-based products (including Truvada), but neither of those studies was powered to draw conclusions by gender. At the same time, it is biologically plausible that the products would not work in women, based on relatively low drug concentration in vaginal tissue associated with Truvada (compared to levels found effective in CAPRISA 004 from a topical tenofovir product, or compared to levels found in rectal tissue in men). Thus, the shortage of efficacy data in women was a curveball for the panel, deciding how broadly to approve the indication for Truvada.
The committee voted 12-8 to approve the wider indication. This close vote signals that the most interesting question, in advance of the FDA's anticipated June 15 decision on labeling, may be the "1(c)" population. FDA appears likely to approve for MSM and serodiscordant couples, perhaps dampening the public debate on these questions--but focusing the debate on the wider indication?
The vote on "Question 1(c)," however (the panel voted on each proposed indication one at a time), was much closer. The question was whether to recommend approval for indication in "Other individuals at risk for acquiring HIV through sexual activity." As a committee member noted before the vote, this question was primarily about heterosexual women, many of whom face a high risk of HIV acquisition in the U.S. (not to mention globally), but in whom the clinical trials data have been less conclusive. It has been widely noted that the FEM-PrEP trial, testing Truvada in heterosexual women, was stopped when an interim review showed that it would not demonstrate efficacy. It has emerged subsequently, however, that adherence in FEM-PrEP was too low for the trial to have demonstrated an effect, regardless of the pill's actual efficacy. Women have been included in other studies of oral tenofovir-based products (including Truvada), but neither of those studies was powered to draw conclusions by gender. At the same time, it is biologically plausible that the products would not work in women, based on relatively low drug concentration in vaginal tissue associated with Truvada (compared to levels found effective in CAPRISA 004 from a topical tenofovir product, or compared to levels found in rectal tissue in men). Thus, the shortage of efficacy data in women was a curveball for the panel, deciding how broadly to approve the indication for Truvada.
The committee voted 12-8 to approve the wider indication. This close vote signals that the most interesting question, in advance of the FDA's anticipated June 15 decision on labeling, may be the "1(c)" population. FDA appears likely to approve for MSM and serodiscordant couples, perhaps dampening the public debate on these questions--but focusing the debate on the wider indication?
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