View source for Bremelanotide

{{Short description|Chemical compound}}
{{Use dmy dates|date=November 2019}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 445399889
| image = Bremelanotide structure.svg
| width = 250
| alt = <!--Clinical data-->
| pronounce = {{IPAc-en|audio=bremelanotide-pronunciation.ogg|ˌ|b|r|ɛ|m|ᵻ|ˈ|l|æ|n|ə|t|aɪ|d}}
| tradename = Vyleesi
| Drugs.com = {{drugs.com|monograph|bremelanotide-acetate}}
| MedlinePlus = a619054
| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| licence_EU = <!-- EMEA requires brand name -->
| DailyMedID = Bremelanotide
| licence_US = <!-- FDA may use generic name -->
| pregnancy_AU = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Subcutaneous injection|Subcutaneous]]<ref name="Vyleesi-Label" />
| class = [[Melanocortin receptor]] [[agonist]]
| ATCvet = 
| ATC_prefix = G02
| ATC_suffix = CX05
| ATC_supplemental = <!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!--Pharmacokinetic data-->| bioavailability = {{abbrlink|SC|Subcutaneous injection}}: ~100%<ref name="Vyleesi-Label" />
| protein_bound = 21%<ref name="Vyleesi-Label" />
| metabolism = [[Hydrolysis]] of [[peptide bond]]s<ref name="Vyleesi-Label" />
| metabolites = 
| onset = 
| elimination_half-life = 2.7 hours<ref name="Vyleesi-Label" />
| duration_of_action = 
| excretion = [[Urine]]: 64.8%<br />[[Feces]]: 22.8%

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 189691-06-3
| CAS_supplemental = 
| PubChem = 9941379
| PubChemSubstance = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB11653
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8116997
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6Y24O4F92S
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D06569
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 2070241
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = PT-141; Rekynda
| USAN = bremelanotide acetate

<!-- Chemical and physical data -->| IUPAC_name = (3''S'',6''S'',9''R'',12''S'',15''S'',23''S'')-15-[(''N''-Acetyl-<small>L</small>-norleucyl)amino]-9-benzyl-6-{3-[(diaminomethylidene)amino]propyl}-12-(1''H''-imidazol-5-ylmethyl)-3-(1''H''-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexaazacyclotricosane-23-carboxylic acid
| C = 50
| H = 68
| N = 14
| O = 10
| SMILES = O=C(C)N[C@@H](CCCC)C(N[C@@H]1C(N[C@@H](CC2=CNC=N2)C(N[C@H](CC3=CC=CC=C3)C(N[C@@H](CCC/N=C(N)\N)C(N[C@@H](CC4=CNC5C=CC=CC45)C(N[C@@H](CCCCNC(C1)=O)C(O)=O)=O)=O)=O)=O)=O)=O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C50H68N14O10/c1-3-4-16-35(58-29(2)65)43(67)64-41-25-42(66)54-20-11-10-18-37(49(73)74)60-46(70)39(23-31-26-56-34-17-9-8-15-33(31)34)62-44(68)36(19-12-21-55-50(51)52)59-45(69)38(22-30-13-6-5-7-14-30)61-47(71)40(63-48(41)72)24-32-27-53-28-57-32/h5-9,13-15,17,26-28,35-41,56H,3-4,10-12,16,18-25H2,1-2H3,(H,53,57)(H,54,66)(H,58,65)(H,59,69)(H,60,70)(H,61,71)(H,62,68)(H,63,72)(H,64,67)(H,73,74)(H4,51,52,55)/t35-,36-,37-,38+,39-,40-,41-/m0/s1
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FFHBJDQSGDNCIV-MFVUMRCOSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}
<!-- Definition and medical uses -->

'''Bremelanotide''', sold under the brand name '''Vyleesi''', is a medication used to treat [[female sexual arousal disorder|low sexual desire in women]].<ref name=AHFS2019/> Specifically it is used for low sexual desire which occurs before [[menopause]] and is not due to medical problems, psychiatric problems, or problems within the relationship.<ref name=FDA2019 /><ref name="FDA Snapshot">{{cite web | title=Drug Trials Snapshots: Vyleesi | website=U.S. [[Food and Drug Administration]] (FDA) | date=12 July 2019 | url=https://www.fda.gov/drugs/drug-safety-and-availability/drug-trials-snapshots-vyleesi | archive-url=https://web.archive.org/web/20191120184724/https://www.fda.gov/drugs/drug-safety-and-availability/drug-trials-snapshots-vyleesi | archive-date=20 November 2019 | url-status=dead | access-date=20 November 2019}}{{PD-notice}}</ref><ref name=AHFS2019/> It is given by an [[subcutaneous injection|injection just under the skin]] of the [[thigh]] or [[abdomen]].<ref name=AHFS2019/><ref name="FDA Snapshot" />

<!-- Side effects and mechanism -->
Common side effects include [[nausea]], [[Injection site pain|pain at the site of injection]], and [[headache]].<ref name=AHFS2019>{{cite web |title=Bremelanotide Acetate Monograph for Professionals |url=https://www.drugs.com/monograph/bremelanotide-acetate.html |website=Drugs.com |access-date=24 October 2019 }}</ref> It may also cause a temporary increase in [[blood pressure]] and decrease in [[heart rate]] after each dose, and [[Hyperpigmentation|darkening of the gums, face, and breasts]].<ref name="FDA Snapshot" /> The medication is a [[peptide]] and acts by [[agonist|activating]] the [[melanocortin receptor]]s.<ref name="Vyleesi-Label">{{cite web | title=Vyleesi- bremelanotide injection | website=[[DailyMed]] | date=10 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9146ae05-918b-483e-b86d-933485ce36eb | access-date=20 November 2019}}</ref><ref name="Kingsberg2015rev">{{cite journal | vauthors = Kingsberg SA, Clayton AH, Pfaus JG | title = The Female Sexual Response: Current Models, Neurobiological Underpinnings and Agents Currently Approved or Under Investigation for the Treatment of Hypoactive Sexual Desire Disorder | journal = CNS Drugs | volume = 29 | issue = 11 | pages = 915–933 | date = November 2015 | pmid = 26519340 | doi = 10.1007/s40263-015-0288-1 | s2cid = 7437096 }}</ref>

<!-- History and culture -->
Bremelanotide was approved for medical use in the United States in 2019.<ref name=AHFS2019/><ref>{{cite web | title=Drug Approval Package: Vyleesi | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210557Orig1s000TOC.cfm | archive-url=https://web.archive.org/web/20191120182943/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/210557Orig1s000TOC.cfm | url-status=dead | archive-date=20 November 2019 }}</ref> It was developed by Palatin Technologies.<ref name="AdisInsight">{{cite web|title=Bremelanotide|url=http://adisinsight.springer.com/drugs/800014146|publisher=AdisInsight|access-date=6 April 2017}}</ref> The US [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]].<ref>{{cite web | title=New Drug Therapy Approvals 2019 | website=U.S. Food and Drug Administration | date=31 December 2019 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | archive-url=https://web.archive.org/web/20200502164101/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2019 | url-status=dead | archive-date=2 May 2020 | access-date=15 September 2020}}</ref>

==Medical uses==
Bremelanotide is used for the treatment of generalized [[hypoactive sexual desire disorder]] (HSDD) in premenopausal women.<ref name=FDA2019 /><ref name="Frellick">{{cite web | vauthors = Frellick M |title=FDA Approves New Libido-Boosting Drug for Premenopausal Women |url=https://www.medscape.com/viewarticle/914779?nlid=130327_3901&src=wnl_newsalrt_190621_MSCPEDIT&uac=194606CT&impID=2003265&faf=1 |website=Medscape |publisher=WebMD LLC |access-date=22 June 2019 }}</ref> Specifically it is only recommended in those who have the condition without an underlying cause, such as medical, psychiatric, or relationship problems.<ref name=FDA2019/><ref name=AHFS2019/>

It should be used at least 45 minutes before anticipated sexual activity.<ref name=FDA2019/> Only one dose per 24 hours or no more than eight doses per month is recommended.<ref name=FDA2019/> It should be stopped after eight weeks if there is no improvement in sexual desire and associated distress.<ref name=FDA2019>{{cite press release | title=FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women | website=U.S. [[Food and Drug Administration]] (FDA) | date=21 June 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-hypoactive-sexual-desire-disorder-premenopausal-women | archive-url=https://web.archive.org/web/20191120183329/https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-hypoactive-sexual-desire-disorder-premenopausal-women | archive-date=20 November 2019 | url-status=dead | access-date=24 October 2019}}{{PD-notice}}</ref>

==Contraindications==
Due to its effects on blood pressure (generally a transient increase in systolic blood pressure by 6{{nbsp}}mmHg, and diastolic blood pressure by 3{{nbsp}}mmHg), bremelanotide is considered contraindicated in people with uncontrolled [[hypertension|high blood pressure]] or cardiovascular disease.<ref name="Vyleesi-Label" /> 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.<ref name="Vyleesi-Label" />

==Side effects==
The most frequently encountered side effect of bremelanotide is [[nausea]] (40.0%), which may be intolerable to some people.<ref name="Vyleesi-Label" /> The use of [[antiemetic|anti-nausea]] medications (e.g., [[ondansetron]]) prior to administration of bremelanotide may help to reduce the nausea.<ref name="Vyleesi-Label" /> Other side effects may include [[flushing (physiology)|flushing]] (20.3%), [[injection site reaction]]s (13.2%), [[headache]] (11.3%), [[vomiting]] (4.8%), [[cough]] (3.3%), [[fatigue (medical)|fatigue]] (3.2%), [[hot flash]]es (2.7%), [[paresthesia]] (2.6%), [[dizziness]] (2.2%), and [[nasal congestion]] (2.1%).<ref name="Vyleesi-Label" /><ref name=Gelman2017rev>{{cite journal | vauthors = Gelman F, Atrio J | title = Flibanserin for hypoactive sexual desire disorder: place in therapy | journal = Therapeutic Advances in Chronic Disease | volume = 8 | issue = 1 | pages = 16–25 | date = January 2017 | pmid = 28203348 | pmc = 5298357 | doi = 10.1177/2040622316679933 }}</ref><ref name=Belkin2015rev/> Discoloration of the skin, specifically [[hyperpigmentation]], may occur—especially if bremelanotide is used more than eight times in one month.<ref name="Vyleesi-Label" /> The discoloration may not resolve upon stopping use of bremelanotide, and may occur on the face, gums, or breasts.<ref name="Vyleesi-Label" /> Experiments in animals, even at high doses, failed to find any negative consequence of bremelanotide on fertility.<ref name="Vyleesi-Label" />

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.<ref>{{cite journal | vauthors = Spana C, Jordan R, Fischkoff S | title = Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials | journal = Diabetes, Obesity & Metabolism | volume = 24 | issue = 6 | pages = 1084–1093 | date = June 2022 | pmid = 35170192 | pmc = 9314948 | doi = 10.1111/dom.14672 }}</ref>
{{Side effects of bremelanotide in phase 3 clinical trials}}

== Interactions ==
Bremelanotide does not meaningfully interact with [[Alcohol (drug)|alcohol]], unlike [[flibanserin]] (for which the interaction with alcohol is a major barrier to its use).<ref>{{cite web | vauthors = Garde D |title=Experimental drug for women revives an intense debate on sexual desire |url=https://www.statnews.com/2019/06/20/women-sex-drive-experimental-drug-bremelanotide/ |website=STAT |access-date=23 June 2019 |date=20 June 2019 }}</ref><ref name="Clayton et al">{{cite journal | vauthors = Clayton AH, Kingsberg SA, Goldstein I | title = Evaluation and Management of Hypoactive Sexual Desire Disorder | journal = Sexual Medicine | volume = 6 | issue = 2 | pages = 59–74 | date = June 2018 | pmid = 29523488 | pmc = 5960024 | doi = 10.1016/j.esxm.2018.01.004 }}</ref> 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 as [[naltrexone]] and [[indomethacin]].<ref name="Vyleesi-Label" />

==Pharmacology==

===Pharmacodynamics===
Bremelanotide is a [[non-selective]] [[agonist]] of the [[melanocortin receptor]]s, [[melanocortin 1 receptor|MC<sub>1</sub>]] through [[melanocortin 5 receptor|MC<sub>5</sub>]] (with the exception of [[melanocortin 2 receptor|MC<sub>2</sub>]], the receptor of {{abbrlink|ACTH|adrenocorticotropic hormone}}), but acting primarily as an [[melanocortin 3 receptor|MC<sub>3</sub>]] and [[melanocortin 4 receptor|MC<sub>4</sub> receptor]] agonist.<ref name=King2007rev>{{cite journal | vauthors = King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H | title = Melanocortin receptors, melanotropic peptides and penile erection | journal = Current Topics in Medicinal Chemistry | volume = 7 | issue = 11 | pages = 1098–1106 | year = 2007 | pmid = 17584130 | pmc = 2694735 | doi = 10.2174/1568026610707011111 | author6-link = Hunter Wessells }}</ref><ref name=Gelman2017rev/><ref name=Kingsberg2015rev/>

===Pharmacokinetics===
The [[bioavailability]] of bremelanotide with [[subcutaneous injection]] is about 100%.<ref name="Vyleesi-Label" /> Following a subcutaneous injection of bremelanotide, [[Cmax (pharmacology)|maximal levels]] occur after about one hour, with a range of 0.5 to 1.0&nbsp;hours.<ref name="Vyleesi-Label" /> The [[plasma protein binding]] of bremelanotide is 21%.<ref name="Vyleesi-Label" /> Bremelanotide is [[metabolism|metabolized]] via [[hydrolysis]] of its [[peptide bond]]s.<ref name="Vyleesi-Label" /> The [[elimination half-life]] of bremelanotide is 2.7&nbsp;hours, with a range of 1.9 to 4.0&nbsp;hours.<ref name="Vyleesi-Label" /> Bremelanotide is [[excretion|excreted]] 64.8% in [[urine]] and 22.8% in [[feces]].<ref name="Vyleesi-Label" />

==Chemistry==
Bremelanotide is a [[cyclic compound|cyclic]] [[heptapeptide]] [[lactam]] [[structural analog|analogue]] of [[α-melanocyte-stimulating hormone]] (α-MSH).<ref name=Belkin2015rev>{{cite journal | vauthors = Belkin ZR, Krapf JM, Goldstein AT | title = Drugs in early clinical development for the treatment of female sexual dysfunction | journal = Expert Opinion on Investigational Drugs | volume = 24 | issue = 2 | pages = 159–167 | date = February 2015 | pmid = 25376023 | doi = 10.1517/13543784.2015.978283 | s2cid = 207477620 }}</ref> It has the [[amino acid sequence]] Ac-Nle-''cyclo''[Asp-His-<small>D</small>-Phe-Arg-Trp-Lys]-OH,<ref name=INN>{{cite journal|title=Proposed INN List 95|journal=WHO Drug Information|date=2006|volume=20|issue=2|page=124|url=https://www.who.int/medicines/publications/druginformation/innlists/PL95.pdf?ua=1}}</ref> and is also known as {{Chem name|''cyclo''-Ac-[Nle<sup>4</sup>,Asp<sup>5</sup>,<small>D</small>-Phe<sup>7</sup>,Lys<sup>10</sup>]α-MSH-(4-10)}} (a substitutional name). Bremelanotide is an [[active metabolite]] of [[melanotan II]] that lacks the [[C-terminus|C-terminal]] [[amide]] [[functional group|group]].<ref name=Hadley2005/>

Aside from melanotan II and endogenous [[melanocyte-stimulating hormone]]s like α-MSH, other peptide analogues of the same family as bremelanotide include [[afamelanotide]] (NDP-α-MSH), [[modimelanotide]], and [[setmelanotide]].

==History==
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 potential [[sunless tanning]] agents. They synthesized and tested several [[Structural analog|analog]]s, including peptides they subsequently named, [[melanotan-I]] and [[melanotan II]].<ref name=King2007rev/><ref name=Hadley2005>{{cite journal | vauthors = Hadley ME | title = Discovery that a melanocortin regulates sexual functions in male and female humans | journal = Peptides | volume = 26 | issue = 10 | pages = 1687–1689 | date = October 2005 | pmid = 15996790 | doi = 10.1016/j.peptides.2005.01.023 | s2cid = 22559801 }}</ref>

Very early in the process one of the scientists, Mac Hadley,<ref name=Hadley2005/> who was conducting experiments on himself with the peptide [[melanotan II]], injected himself with twice the dose he intended and experienced an [[Priapism|eight-hour erection]], along with nausea and vomiting.<ref name=King2007rev/>

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,<ref>{{cite news|title=EpiTan focuses on Melanotan, a potential blockbuster|url=https://www.thepharmaletter.com/article/epitan-focuses-on-melanotan-a-potential-blockbuster|work=The Pharma Letter|date=1 November 2004}}</ref><ref name=HadleyDorr2006>{{cite journal | vauthors = Hadley ME, Dorr RT | title = Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization | journal = Peptides | volume = 27 | issue = 4 | pages = 921–930 | date = April 2006 | pmid = 16412534 | doi = 10.1016/j.peptides.2005.01.029 | s2cid = 21025287 }}</ref> which changed its name to Clinuvel in 2006.<ref>{{cite news|title=Epitan changes name to Clinuvel, announces new clinical program|url=http://www.labonline.com.au/content/life-scientist/news/epitan-changes-name-to-clinuvel-announces-new-clinical-program-161764385|work=LabOnline|date=27 February 2006}}</ref>

To pursue the sexual dysfunction agent, melanotan II was licensed by Competitive Technologies to Palatin Technologies.<ref name=Hadley2005/> 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.<ref name=King2007rev/><ref name=Litigation/> Competitive Technologies sued Palatin for breach of contract and to try to claim ownership of bremelanotide;<ref name=Litigation>{{cite press release|title=Palatin Technologies Refutes Competitive Technologies Contention of Material Breach|url=http://www.prnewswire.com/news-releases/palatin-technologies-refutes-competitive-technologies-contention-of-material-breach-58006787.html|publisher=Palatin Technologies|date=12 September 2007|access-date=6 April 2017|archive-url=https://web.archive.org/web/20170407055315/http://www.prnewswire.com/news-releases/palatin-technologies-refutes-competitive-technologies-contention-of-material-breach-58006787.html|archive-date=7 April 2017|url-status=dead}}</ref> the parties settled in 2008, with Palatin retaining rights to bremelanotide, returning rights to melanotan-II to Competitive Technologies, and paying $800,000.<ref>{{cite press release|title=Palatin Technologies Announces Litigation Settlement With Competitive Technologies|url=http://www.prnewswire.com/news-releases/palatin-technologies-announces-litigation-settlement-with-competitive-technologies-57107302.html|publisher=Palatin Technologies|date=22 January 2008|access-date=6 April 2017|archive-url=https://web.archive.org/web/20170406204527/http://www.prnewswire.com/news-releases/palatin-technologies-announces-litigation-settlement-with-competitive-technologies-57107302.html|archive-date=6 April 2017|url-status=dead}}</ref>

In August 2004, Palatin signed an agreement with [[King Pharmaceuticals]] to co-develop bremelanotide in the US and jointly license it outside the US; King paid Palatin $20M upfront.<ref>{{cite web|title=Form 10-K for the year ended June 30, 2004|url=https://www.sec.gov/Archives/edgar/data/911216/000108802004000046/form10-k_063004.htm|publisher=Palatin via SEC EDGAR|date=13 September 2004}}</ref>

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.<ref name=Lodise2013rev>{{cite journal | vauthors = Lodise NM | title = Hypoactive sexual desire disorder in women: treatment options beyond testosterone and approaches to communicating with patients on sexual health | journal = Pharmacotherapy | volume = 33 | issue = 4 | pages = 411–421 | date = April 2013 | pmid = 23553810 | doi = 10.1002/phar.1209 | s2cid = 206357650 }}</ref><ref name=Gelman2017rev/><ref name=Ückert2014rev>{{cite journal | vauthors = Ückert S, Bannowsky A, Albrecht K, Kuczyk MA | title = Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies | journal = Expert Opinion on Investigational Drugs | volume = 23 | issue = 11 | pages = 1477–1483 | date = November 2014 | pmid = 25096243 | doi = 10.1517/13543784.2014.934805 | s2cid = 22665242 }}</ref> Four trials were conducted in ED, the last being a Phase IIb published in 2008.<ref name=Ückert2014rev/> King terminated the co-development agreement shortly after the FDA halted the trials.<ref>{{cite news| vauthors = Nagle M |title=Erectile dysfunction drug deemed a flop|url=http://www.outsourcing-pharma.com/Preclinical-Research/Erectile-dysfunction-drug-deemed-a-flop|work=Outsourcing Pharma|date=10 September 2007 }}</ref>

The drug was then [[Pharmaceutical formulation|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.<ref name=Kingsberg2015rev/><ref name=Belkin2015rev/> Palatin launched the Phase III trials with bremelanotide administered via an [[autoinjector]].<ref name=10K2015/>

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.<ref name=10K2015>{{cite web|title=Palatin 10K for the fiscal year ended June 30, 2015|url=https://www.sec.gov/Archives/edgar/data/911216/000135448815004334/ptn_10k.htm|publisher=Palatin via SEC EDGAR|date=18 September 2015}}</ref>

In November 2016, Palatin announced results of the Phase III trials, and shortly thereafter began seeking a partner to complete development in the US.<ref>{{cite news|agency=Reuters|title=Female Viagra: Drugmaker Palatin Is Looking for a Buyer|url=http://fortune.com/2016/11/02/female-viagra-addyi-palatin/|work=[[Fortune (magazine)|Fortune]]|date=2 November 2016}}</ref> 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.<ref>{{cite news|title=AMAG Pharma closes deal for North America rights to Rekynda|url=https://www.thepharmaletter.com/article/amag-pharma-closes-deal-for-north-america-rights-to-rekynda|work=The Pharma Letter|date=2 February 2017}}</ref>

A [[New Drug Application]] of bremelanotide for female sexual dysfunction was accepted by the US [[Food and Drug Administration]] (FDA) in June 2018, with a [[Prescription Drug User Fee Act]] (PDUFA) goal date set for 23 March 2019.<ref>{{Cite web|url=http://www.mdmag.com/medical-news/fda-accepts-bremelanotide-nda-for-treatment-of-hypoactive-sexual-desire-disorder|title=Press release: FDA Accepts Bremelanotide NDA for Treatment of Hypoactive Sexual Desire Disorder|website=MD Magazine|access-date=2018-06-27}}</ref> It was approved for use in the United States in June 2019.<ref name=FDA2019 /><ref>{{cite web | vauthors = Nedelman M |title=FDA approves new drug for women with low sexual desire disorder |url=https://www.cnn.com/2019/06/21/health/women-sexual-desire-drug-bremelanotide-vyleesi-bn/index.html |publisher=[[CNN]] |date=21 June 2019 |access-date=23 June 2019 }}</ref><ref name=WP-FDA>{{Cite news| vauthors = Cha AE, McGinley L | title=A new 'female Viagra' approved by FDA despite skepticism| newspaper=[[The Washington Post]]| url=https://www.washingtonpost.com/health/2019/06/21/new-female-viagra-approved-by-fda-despite-skepticism/ | date=21 June 2019| access-date=21 June 2019 }}</ref>

== References ==
{{Reflist}}

{{Sexual dysfunction pharmacotherapies}}
{{Melanocortin receptor modulators}}
{{Portal bar | Medicine}}

[[Category:Aphrodisiacs]]
[[Category:Female sexual dysfunction drugs]]
[[Category:Melanocortin receptor agonists]]
[[Category:Heptapeptides]]
[[Category:Cyclic peptides]]