Stephanie Fox-Rawlings, PhD, National Center for Health Research, August 7, 2019
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.
A new treatment to prevent HIV infection could be beneficial, considering the safety concerns of the currently available PrEP treatment. However, Descovy would only provide a benefit if it is as at least as effective and safe as Truvada for each population for which it is indicated. Otherwise, users could be at an unnecessarily increased risk for HIV.
The DISCOVER Trial found similar rates of protection against HIV infection among participants taking Descovy or Truvada. While the trial seems well designed to demonstrate comparative effectiveness of these two drugs, it is still a single trial. Replication is the key to scientific evidence. Independent trials could result in different infection rates due to differences in the demographic or treatment profiles of patients or other factors.
For example, study participants were more likely to be white, older, and better educated that the general US population that is at risk for HIV – which is the target audience for the drug. While this population may be consistent with people who currently use Truvada, there are questions about the generalizability of the data to the whole population who could consider using this drug. It is important to study the general US population that is at risk for HIV.
The study also found improvements for biomarkers related to kidney health and bone density, suggesting that Descovy was safer than Truvada. However, this is only relevant if it translates to clinically meaningful differences in the number of adverse events related to kidneys and bone fractures, which were similar in both treatment groups in the clinical trial.
The trial suggested that the benefits outweighed the risk for men who have sex with men. However, the benefit-risk ratio was less clear for transgender women. This is due, in part, to the relatively low number of transgender women in the trial, the high drop-out rate, and the lack of subgroup analysis. If FDA is considering approving Descovy for transgender women, then the efficacy and safety of Descovy for transgender women should be analyzed. This is especially important given the recent findings that feminizing hormone therapy can interact with PrEP drugs.
Similarly, there is insufficient evidence that Descovy is effective and safe for PrEP for cis-gendered women or adolescents. There are too many unanswered questions regardingthe levels of drug achieved in relevant tissues and the amount needed to consider extrapolation for PrEP use for cis-gendered women and girls. Similarly, the benefits and risks for adolescent boys differs from that of men, and should be considered separately. Clinical trials demonstrating effectiveness and safety for cis-gendered women and adolescents are needed if the FDA is considering approving Descovy for them.
We understand the desire to provide a new PrEP treatment indicated for a broad population, especially when that new treatment is expected to potentially have fewer risks for kidneys and bone density. However, it is inappropriate and potentially dangerous to approve this drug for subgroups of patients that haven’t been adequately studied. The FDA law requires substantial evidence that the benefits outweigh the risks for each subpopulation that the new indication would include.
Thank you.
On the question of whether there was substantial evidence for the safety and effectiveness of Descovy for PrEP for men and transgendered women who have sex with men, the committee voted in favor (16 for and 2 against). O the question of whether there was sufficient rational to expand the indication for PrEP for cisgender women (to include cisgender women in the approval), the committee voted against (8 for and 10 against). You can read more about the meeting here.
On October 3, 2019, FDA approved the new indication for PrEP. The indication excludes protection for receptive vaginal sex. You can read FDA’s press release here.