|Pronunciation||// ( listen)|
|Trade names||Rekynda (tentative)|
|Elimination half-life||120 minutes|
|Chemical and physical data|
|Molar mass||1025.2 g/mol|
|3D model (JSmol)|
|(what is this?)|
Bremelanotide (tentative brand name Vyleesi; former developmental code name PT-141) is a peptide melanocortin receptor agonist which is under development by Palatin Technologies as a treatment for female sexual dysfunction.
Bremelanotide is a non-selective agonist of the melanocortin receptors, MC1 through MC5 (with the exception of MC2, the receptor of ACTH), but acting primarily as an MC3 and MC4 receptor agonist.
Bremelanotide is a cyclic heptapeptide lactam analogue of α-melanocyte-stimulating hormone (α-MSH). It has the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, and is also known as cyclo-[Nle4,Asp5,D-Phe7,Lys10]α-MSH-(4-10). Bremelanotide is an active metabolite of melanotan II that lacks the C-terminal amide group.
Research in the early 1960s showed that in rats, administration of α-MSH caused sexual arousal, and work on this continued in many labs up through the 1980s, when scientists at University of Arizona began attempting to develop α-MSH and analogs as potential sunless tanning agents, and synthesized and tested several analogs, including melanotan-I and melanotan II.
Very early in the process one of the scientists, Mac Hadley, who was conducting experiments on himself with an early tool compound, melanotan II, injected himself with twice the dose he intended and experienced an eight-hour erection, along with nausea and vomiting.
To pursue the tanning agent, melanotan-I was licensed by Competitive Technologies, a technology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan, which changed its name to Clinuvel in 2006.
To pursue the sexual dysfunction agent, melanotan-II was licensed by Competitive Technologies to Palatin Technologies. Palatin ceased development of melanotan-II in 2000 and synthesized, patented, and began to develop bremelanotide, a likely metabolite of melanotan-II that differs from melanotan-II in that it has a hydroxyl group where melanotan-II has an amide. Competitive Technologies sued Palatin for breach of contract and to try to claim ownership of bremelanotide; the parties settled in 2008 with Palatin retaining rights to bremelanotide, returning rights to melanotan-II to Competitive Technologies, and paying $800,000.
Palatin conducted Phase II trials of intranasal bremelanotide in both female sexual dysfunction (FSD) and male erectile dysfunction (ED) but these trials were halted by the FDA in 2007 due to increased blood pressure in clinical trial subjects; Palatin stopped development of the intranasal formulation in 2008. Four trials were conducted in ED, the last being a Phase IIb published in 2008. King terminated the co-development agreement shortly after the FDA halted the trials.
The drug was then reformulated to be delivered by injection and trials continued in FSD. A phase II dose-finding trial in FSD in which the drug was administered 45 minutes before sex showed promise at the highest dose and only transient signs of high blood pressure; two Phase III trials were launched at the end of 2014. Palatin launched the Phase III trials with bremelanotide administered via an autoinjector.
In 2014 Palatin licensed European rights to bremelanotide to Gedeon Richter Plc. for around $10 million, and Palatin received a milestone payment of around $3 million when it started the Phase III trials in the US. In September 2016 Palatin and Gedeon RIchter terminated that agreement.
In November 2016 Palatin announced results of the Phase III trials, and shortly thereafter began seeking a partner to complete development in the US. In January 2017 Palatin and AMAG Pharmaceuticals agreed that AMAG exclusively would complete development and market bremelanotide in North America and the two would work together to license it in other territories; AMAG agreed to pay $60 million upfront, up to $80 million in regulatory milestones, up to $300 million in sales milestones, and tiered royalties ranging from high single digit to low double digit percentages.
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