Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder
Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH
Obstetrics and Gynecology (2019) · n=684
52-week open-label extension of the RECONNECT phase-3 trials — 684 women received bremelanotide for up to 76 weeks total, with nausea (40.4%), flushing (20.6%), and headache (12.0%) the most common adverse events and no new safety signals beyond the on-demand-use profile already established in the core trials.
This is the long-term safety and efficacy extension paper that supports the FDA-approved chronic-use framing of bremelanotide / Vyleesi for hypoactive sexual desire disorder, published alongside the core RECONNECT phase-3 efficacy paper in the November 2019 Obstetrics and Gynecology HSDD issue. Of 856 women eligible from the core RECONNECT trials (the same 1,267-patient trial pair anchored elsewhere on this site by Kingsberg 2019), 684 enrolled in the open-label extension and 272 completed it. Participants received bremelanotide 1.75 mg subcutaneously on demand, up to 12 doses per 4-week period and not more than one dose per 24 hours, for up to 52 additional weeks following the 24-week double-blind core phase — yielding up to 76 weeks of total on-drug exposure. The treatment-emergent adverse event profile in the open-label extension was consistent with the core phase: nausea (40.4%), flushing (20.6%), and headache (12.0%) were the most common drug-related adverse events, with nausea the only severe adverse event reported by more than one participant. No new safety signals emerged in the extension period beyond those characterized in the regulatory dossier, and patients who continued on bremelanotide sustained the improvements in sexual desire and reductions in associated distress that they had achieved during the double-blind phase. The paper is the longitudinal evidence base that the FDA cited in support of the chronic-use framing for an on-demand medication; without this dataset, the label would have been restricted to shorter treatment durations.
The extension is open-label rather than blinded; both efficacy persistence and patient-reported tolerability are subject to expectation bias in a way that the placebo-controlled core RECONNECT trials addressed but this extension does not. Only 272 of 684 women completed the full 52-week extension, a 40% completion rate that reflects the on-demand-use profile and the high gastrointestinal tolerability burden — nausea at 40.4% is the dominant real-world limiting factor for Vyleesi adherence and is the chief reason the drug has not achieved market penetration comparable to flibanserin or testosterone-based off-label HSDD treatment. The trial does not address chronic daily dosing at any frequency higher than the FDA-approved on-demand cadence, so any biohacker use that exceeds the labeled frequency sits outside the safety dataset reported here. Industry sponsorship by Palatin Technologies and AMAG Pharmaceuticals (then Vyleesi's commercial partner) is disclosed, and several authors are Palatin/AMAG employees; the safety endpoints are predefined and methodologically standard, but the paper is part of the regulatory dossier rather than independent post-marketing surveillance. Long-term cardiovascular safety, particularly chronic blood-pressure effects, is touched on but is the subject of a separate post-marketing requirement that this paper does not fully discharge.
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