What are the long‑term safety data for bremelanotide (PT‑141) in women beyond 24 weeks?
Executive summary
Long‑term clinical trial data for bremelanotide (PT‑141) beyond 24 weeks come primarily from a 52‑week open‑label extension of the 24‑week RECONNECT phase‑3 trials—yielding safety information up to a total of 76 weeks for some participants—with the study authors reporting no new safety signals overall [1]. However, meaningful caveats exist: significant attrition during the extension, at least one case of severe drug‑associated hepatitis, and signals for common adverse effects (notably nausea and transient blood‑pressure increases) that constrain interpretation and wider generalization [2] [3] [4].
1. What the longest trials actually measured and for how long
The pivotal phase‑3 program consisted of two 24‑week randomized, double‑blind trials followed by a 52‑week open‑label extension that allowed participants who completed the core phase and had not suffered serious adverse events to continue bremelanotide on an as‑needed basis, producing safety data for some patients out to a cumulative 76 weeks (24 + 52) [1] [5]. The extension’s headline conclusion—“no new safety signals” compared with the core phase—originates from these open‑label data [1].
2. Common, reproducible safety findings beyond the short term
Across trials and the extension, the most consistent adverse effect is nausea, experienced by a large minority of participants (reported rates around 40% in pooled reports), though relatively few discontinued therapy for this reason (about 8.1% in one pooled analysis) [3]. Transient increases in systolic (~6 mmHg) and diastolic (~3 mmHg) blood pressure were also reproducibly observed, informing contraindications for people with uncontrolled hypertension or cardiovascular disease [4] [3]. The approved dosing limits—no more than one dose per 24 hours and typically no more than eight doses per month—are informed by these hemodynamic and tolerability findings [4] [6].
3. Rare but serious hepatic signal and other severe events
Although authors of the long‑term report state there were “no other new safety signals” overall, LiverTox highlights that among the 684 patients who enrolled in the open‑label extension (272 completed it), one patient developed clinically apparent acute hepatitis after approximately one year of therapy, with aminotransferases rising >20× upper‑limit‑normal and bilirubin about twice normal; minor enzyme elevations persisted at six months but not at 12 months follow‑up [2]. LiverTox also notes prior reports of mild serum enzyme elevations during therapy and the implication—albeit rare—of bremelanotide in clinically apparent acute liver injury [2]. The trials did not identify a cluster of liver events, but the single severe case prevents declaring hepatic safety unequivocally for prolonged use [2].
4. Limitations and biases that shape “long‑term” conclusions
The extension study is open‑label and subject to selection bias because only participants who completed the double‑blind core and had not experienced serious adverse events were eligible to enroll; additionally, more than half of extension enrollees did not complete the year‑long extension (684 enrolled vs 272 completers), which reduces confidence in rare‑event detection and long‑term tolerability estimates [2]. Independent reviewers have also questioned the clinical relevance of some endpoints and effect sizes in the core trials, which matters when balancing benefit against prolonged exposure to known adverse effects like nausea and blood‑pressure changes [4] [7].
5. Practical takeaway and outstanding gaps
Available trial data support that bremelanotide’s safety profile remains broadly stable out to roughly 76 weeks for selected premenopausal women who tolerated the initial 24 weeks, with common transient side effects (nausea, flushing, transient BP rise) and rare but serious hepatic injury reported [1] [3] [2]. Crucially, long‑term safety beyond approximately one year is not well characterized, the open‑label design and attrition limit generalizability, and clinicians must weigh cardiovascular and hepatic cautions when prescribing [2] [4]. Further controlled, prospective long‑term surveillance would be required to quantify rare adverse events and outcomes in broader, real‑world populations [2] [8].