Bremelanotide trials show high discontinuation and patient preference for placebo in HSDD re-analysis
Background
Hypoactive Sexual Desire Disorder (HSDD) is characterized by a persistent lack of sexual desire, causing distress. Previous research led to two large Phase III trials of bremelanotide (PT-141), a melanocortin receptor agonist, as a potential treatment. The original publication of these trial results, by Kingsberg et al., suggested efficacy. However, concerns were raised about the transparency and completeness of the data reporting, as a significant number of protocol-listed outcomes were omitted in favor of unlisted, post-hoc measures. This re-analysis was prompted by the need to critically evaluate the drug's true benefit-risk profile using the full dataset submitted to the FDA.
Study Design
This study performed a meta-analysis of data from two 24-week, Phase III clinical trials of bremelanotide for premenopausal women with HSDD. The analysis was based on the complete dataset from the FDA New Drug Application, not the previously published, incomplete summary by Kingsberg et al. The re-analysis focused on outcomes omitted from the original publication, specifically adverse event-induced study discontinuation and participant preference, measured by the combined outcome of trial completion and subsequent enrollment in a follow-up open-label study.
Results
The meta-analysis confirmed that bremelanotide had modest benefits, similar to the original report, but uncovered significant negative findings that were not disclosed. The odds of discontinuing the study due to an adverse event were substantially higher for participants on bremelanotide compared to placebo (OR = 11.98, 95% CI = 3.74-38.37). The number needed to harm (NNH), representing one additional discontinuation due to an adverse event, was only 6. Furthermore, a combined measure of trial completion and willingness to enter the open-label extension study revealed a strong participant preference for placebo.
Participants on bremelanotide were significantly less likely to both complete the trial and opt into the follow-up study compared to the placebo group (OR = 0.30, 95% CI = .24-.38), with an NNH of 4. Critically, the original publication by Kingsberg et al. failed to report 72.72% of the protocol-listed outcomes, instead presenting results for 15 secondary measures that were not listed in the original study protocols and lacked cited evidence of validity.
Key Findings
- Participants on bremelanotide had an 11.98-fold higher odds of discontinuing the study due to adverse events (NNH: 6).
- Participants showed a strong preference for placebo, being significantly less likely to complete the trial and continue into an open-label study (OR = 0.30, NNH: 4).
- The original trial publication failed to report 72.72% of the outcomes listed in the study protocol.
- The original authors reported on 15 secondary measures that were not listed in the study protocols and lacked evidence of validity.
Why It Matters
This re-analysis provides a crucial counter-narrative to the initial positive reporting on bremelanotide for HSDD. For clinicians and potential users, it highlights that the drug's modest benefits on desire may not outweigh its significant tolerability issues. The finding that participants effectively 'voted with their feet' by discontinuing treatment and avoiding further use is a powerful real-world indicator of the drug's utility. The high rate of adverse event-driven discontinuation (NNH: 6) and clear preference for placebo suggest that bremelanotide is not a broadly useful treatment for HSDD in its studied form. This work also underscores the importance of transparent and complete data reporting in clinical trials, as selective reporting can create a misleading impression of a drug's efficacy and safety profile. Researchers and clinicians should critically assess original trial publications against full FDA data submissions when available.
TitrateLab articles covering PT-141
Written by TitrateLab, separately from the study summarized above.
