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| Pronunciation | /ˌbrɛmɪˈlænətaɪd/ ⓘ |
| Trade names | Vyleesi |
| Other names | PT-141; Rekynda, bremelanotide acetate (USANUS) |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a619054 |
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| Routes of administration | Subcutaneous[1] |
| Drug class | Melanocortin receptoragonist |
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| Pharmacokinetic data | |
| Bioavailability | SCTooltip Subcutaneous injection: ~100%[1] |
| Protein binding | 21%[1] |
| Metabolism | Hydrolysis ofpeptide bonds[1] |
| Eliminationhalf-life | 2.7 hours[1] |
| Excretion | Urine: 64.8% Feces: 22.8% |
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| Chemical and physical data | |
| Formula | C50H68N14O10 |
| Molar mass | 1025.182 g·mol−1 |
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Bremelanotide, sold under the brand nameVyleesi, is a medication used to treatlow sexual desire in women.[2] Specifically it is used for low sexual desire which occurs beforemenopause and is not due to medical problems, psychiatric problems, or problems within the relationship.[3][4][2] It is given by aninjection just under the skin of thethigh orabdomen.[2][4]
Common side effects includenausea,pain at the site of injection, andheadache.[2] It may also cause a temporary increase inblood pressure and decrease inheart rate after each dose, anddarkening of the gums, face, and breasts.[4] The medication is apeptide and acts byactivating themelanocortin receptors.[1][5]
Bremelanotide was approved for medical use in the United States in 2019.[2][6] It was developed by Palatin Technologies.[7] The USFood and Drug Administration (FDA) considers it to be afirst-in-class medication.[8]
Bremelanotide is used for the treatment of generalizedhypoactive sexual desire disorder (HSDD) in premenopausal women.[3][9] Specifically it is only recommended in those who have the condition without an underlying cause, such as medical, psychiatric, or relationship problems.[3][2]
It should be used at least 45 minutes before anticipated sexual activity.[3] Only one dose per 24 hours or no more than eight doses per month is recommended.[3] It should be stopped after eight weeks if there is no improvement in sexual desire and associated distress.[3]
Due to its effects on blood pressure (generally a transient increase in systolic blood pressure by 6 mmHg, and diastolic blood pressure by 3 mmHg), bremelanotide is considered contraindicated in people with uncontrolledhigh blood pressure or cardiovascular disease.[1] As long as bremelanotide is not used more than once in one day, it is not expected to cause more severe increases in blood pressure.[1]
The most frequently encountered side effect of bremelanotide isnausea (40.0%), which may be intolerable to some people.[1] The use ofanti-nausea medications (e.g.,ondansetron) prior to administration of bremelanotide may help to reduce the nausea.[1] Other side effects may includeflushing (20.3%),injection site reactions (13.2%),headache (11.3%),vomiting (4.8%),cough (3.3%),fatigue (3.2%),hot flashes (2.7%),paresthesia (2.6%),dizziness (2.2%), andnasal congestion (2.1%).[1][10][11] Discoloration of the skin, specificallyhyperpigmentation, may occur—especially if bremelanotide is used more than eight times in one month.[1] The discoloration may not resolve upon stopping use of bremelanotide, and may occur on the face, gums, or breasts.[1] Experiments in animals, even at high doses, failed to find any negative consequence of bremelanotide on fertility.[1]
An analysis of clinical trials found that obese women reduced their calorie intake and lost weight. Another drug with a similar mechanism of action (setmelanotide) is approved for weight loss in rare types of obesity.[12]
| Side effect | Placebo (n = 620) | Bremelanotide 1.75 mg (n = 627) | ||
|---|---|---|---|---|
| n | % | n | % | |
| Nausea | 8 | 1.3 | 251 | 40.0 |
| FlushingTooltip Flushing_(physiology) | 2 | 0.3 | 127 | 20.3 |
| Headache | 12 | 1.9 | 71 | 11.3 |
| Injection site reaction | 3 | 0.5 | 34 | 5.4 |
| Vomiting | 1 | 0.2 | 30 | 4.8 |
| Cough | 8 | 1.3 | 21 | 3.3 |
| Fatigue | 3 | 0.5 | 20 | 3.2 |
| Injection site erythema | 1 | 0.2 | 18 | 2.9 |
| Hot flush | 1 | 0.2 | 17 | 2.7 |
| Paresthesia | 0 | 0.0 | 16 | 2.6 |
| Dizziness | 3 | 0.5 | 14 | 2.2 |
| Injection site pruritus | 1 | 0.2 | 13 | 2.1 |
| Abdominal pain | 4 | 0.6 | 12 | 1.9 |
| Myalgia | 1 | 0.2 | 11 | 1.8 |
| Summary:Side effects ofbremelanotide with a ≥1% incidence in a combined analysis of two phase 3, double-blind, placebo controlled-clinical trials evaluating safety and efficacy at a daily dosage of 1.75 mg.Nausea was very common and occurred after a median time of 30 minutes for a median duration of 2.4 hours. "Across both studies, seven patients who receivedbremelanotide reported 10 treatment-emergent serious adverse events, and three patients who receivedplacebo reported four treatment-emergent serious adverse events." Mostside effects were reported to be transient and were "mild or moderate in intensity".Bremelanotide had a "favourable" safety profile.Sources: See template. | ||||
Bremelanotide does not meaningfully interact withalcohol, unlikeflibanserin (for which the interaction with alcohol is a major barrier to its use).[13][14] However, bremelanotide does interact with certain medications that people take by mouth. By slowing gastric motility, bremelanotide is thought to reduce the oral absorption (bioavailability) of certain medications, such asnaltrexone andindomethacin.[1]
Bremelanotide is anon-selectiveagonist of themelanocortin receptors,MC1 throughMC5 (with the exception ofMC2, the receptor ofACTHTooltip adrenocorticotropic hormone), but acting primarily as anMC3 andMC4 receptor agonist.[15][10][5]
Thebioavailability of bremelanotide withsubcutaneous injection is about 100%.[1] Following a subcutaneous injection of bremelanotide,maximal levels occur after about one hour, with a range of 0.5 to 1.0 hours.[1] Theplasma protein binding of bremelanotide is 21%.[1] Bremelanotide ismetabolized viahydrolysis of itspeptide bonds.[1] Theelimination half-life of bremelanotide is 2.7 hours, with a range of 1.9 to 4.0 hours.[1] Bremelanotide isexcreted 64.8% inurine and 22.8% infeces.[1]
Bremelanotide is acyclicheptapeptidelactamanalogue ofα-melanocyte-stimulating hormone (α-MSH).[11] It has theamino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH,[16] and is also known ascyclo-Ac-[Nle4,Asp5,D-Phe7,Lys10]α-MSH-(4-10) (a substitutional name). Bremelanotide is anactive metabolite ofmelanotan II that lacks theC-terminalamidegroup.[17]
Aside from melanotan II and endogenousmelanocyte-stimulating hormones like α-MSH, other peptide analogues of the same family as bremelanotide includeafamelanotide (NDP-α-MSH),modimelanotide, andsetmelanotide.
Studies in the early 1960s showed that administration of α-MSH caused sexual arousal in rats, sparking interest in α-MSH. In the 1980s, scientists at University of Arizona began developing α-MSH and analogs as potentialsunless tanning agents. They synthesized and tested severalanalogs, including peptides they subsequently named,melanotan-I andmelanotan II.[15][17]
Very early in the process one of the scientists, Mac Hadley,[17] who was conducting experiments on himself with the peptidemelanotan II, injected himself with twice the dose he intended and experienced aneight-hour erection, along with nausea and vomiting.[15]
To pursue the tanning agent, melanotan-I was licensed by Competitive Technologies, atechnology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan,[18][19] which changed its name to Clinuvel in 2006.[20]
To pursue the sexual dysfunction agent, melanotan II was licensed by Competitive Technologies to Palatin Technologies.[17] 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.[15][21] Competitive Technologies sued Palatin for breach of contract and to try to claim ownership of bremelanotide;[21] the parties settled in 2008, with Palatin retaining rights to bremelanotide, returning rights to melanotan-II to Competitive Technologies, and paying $800,000.[22]
In August 2004, Palatin signed an agreement withKing Pharmaceuticals to co-develop bremelanotide in the US and jointly license it outside the US; King paid Palatin $20M upfront.[23]
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 increasedblood pressure in clinical trial subjects; Palatin stopped development of the intranasal formulation in 2008.[24][10][25] Four trials were conducted in ED, the last being a Phase IIb published in 2008.[25] King terminated the co-development agreement shortly after the FDA halted the trials.[26]
The drug was thenreformulated 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.[5][11] Palatin launched the Phase III trials with bremelanotide administered via anautoinjector.[27]
In 2014, Palatin licensed European rights to bremelanotide toGedeon 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.[27]
In November 2016, Palatin announced results of the Phase III trials, and shortly thereafter began seeking a partner to complete development in the US.[28] In January 2017, Palatin andAMAG 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.[29]
ANew Drug Application of bremelanotide for female sexual dysfunction was accepted by the USFood and Drug Administration (FDA) in June 2018, with aPrescription Drug User Fee Act (PDUFA) goal date set for 23 March 2019.[30] It was approved for use in the United States in June 2019.[3][31][32]
This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain.
