Rhythm Pharmaceuticals Announces Orphan Drug Designation Granted to Setmelanotide for Treatment of Hypothalamic Obesity in Japan
Rhythm Pharmaceuticals (RYTM) has received orphan drug designation from Japan's Ministry of Health for setmelanotide, targeting acquired hypothalamic obesity treatment. Setmelanotide, an MC4R agonist designed to treat hyperphagia and obesity, is currently being evaluated in a global Phase 3 trial with topline data expected in Q2 2025.
The designation highlights the significant unmet medical need in Japan, where an estimated 5,000 to 8,000 patients live with acquired hypothalamic obesity. The condition affects approximately 5,000-10,000 people in the U.S. and 3,500-10,000 in the E.U. This rare disease typically occurs following hypothalamic injury from brain tumors, traumatic brain injury, stroke, or inflammation.
The orphan designation in both Japan and Europe positions Rhythm to potentially deliver the first-ever treatment targeting the underlying biology of hypothalamic obesity, pending successful Phase 3 trial results and regulatory approvals.
Rhythm Pharmaceuticals (RYTM) ha ricevuto la designazione di farmaco orfano dal Ministero della Salute giapponese per setmelanotide, mirato al trattamento dell'obesità ipotalamica acquisita. Setmelanotide, un agonista dell'MC4R progettato per trattare l'iperfagia e l'obesità, è attualmente in fase di valutazione in uno studio di Fase 3 a livello globale, con dati preliminari attesi nel secondo trimestre del 2025.
Questa designazione evidenzia il significativo bisogno medico non soddisfatto in Giappone, dove si stima che 5.000-8.000 pazienti vivano con obesità ipotalamica acquisita. La condizione colpisce circa 5.000-10.000 persone negli Stati Uniti e 3.500-10.000 nell'UE. Questa malattia rara si verifica tipicamente dopo un infortunio ipotalamico causato da tumori cerebrali, trauma cranico, ictus o infiammazione.
La designazione orfana sia in Giappone che in Europa posiziona Rhythm per potenzialmente offrire il primo trattamento mai esistito che mira alla biologia sottostante dell'obesità ipotalamica, in attesa di risultati favorevoli dello studio di Fase 3 e approvazioni regolatorie.
Rhythm Pharmaceuticals (RYTM) ha recibido la designación de medicamento huérfano del Ministerio de Salud de Japón para setmelanotide, dirigido al tratamiento de la obesidad hipotalámica adquirida. Setmelanotide, un agonista de MC4R diseñado para tratar la hiperfagia y la obesidad, se está evaluando actualmente en un ensayo de Fase 3 a nivel global, con datos preliminares esperados para el segundo trimestre de 2025.
La designación destaca la significativa necesidad médica no satisfecha en Japón, donde se estima que 5.000 a 8.000 pacientes viven con obesidad hipotalámica adquirida. La condición afecta aproximadamente a 5.000-10.000 personas en EE. UU. y a 3.500-10.000 en la UE. Esta enfermedad rara suele ocurrir tras una lesión hipotalámica por tumores cerebrales, traumatismos craneales, accidentes cerebrovasculares o inflamación.
La designación huérfana tanto en Japón como en Europa posiciona a Rhythm para potencialmente ofrecer el primer tratamiento que aborde la biología subyacente de la obesidad hipotalámica, a la espera de resultados exitosos del ensayo de Fase 3 y aprobaciones regulatorias.
리듬 제약 (RYTM)은 일본 보건복지부로부터 세트멜라노타이드에 대해 고아약 지정 승인을 받았습니다. 이는 후천성 시상하부 비만 치료를 목표로 하고 있습니다. 세트멜라노타이드는 과식증과 비만을 치료하기 위해 설계된 MC4R 작용제로, 현재 글로벌 3상 임상시험에서 평가되고 있으며, 2025년 2분기에 주요 데이터가 예상됩니다.
이 지정은 일본에서 5,000에서 8,000명의 환자가 후천성 시상하부 비만으로 고통받고 있다는 중요한 의료적 필요를 강조합니다. 이 질환은 미국에서 약 5,000-10,000명, 유럽연합에서 3,500-10,000명에게 영향을 미칩니다. 이 희귀 질환은 일반적으로 뇌종양, 외상성 뇌손상, 뇌졸중 또는 염증으로 인한 시상하부 손상 후에 발생합니다.
일본과 유럽에서의 고아약 지정은 리듬이 시상하부 비만의 근본 생물학을 목표로 하는 최초의 치료제를 제공할 수 있는 가능성을 열어줍니다. 이는 3상 임상시험 결과와 규제 승인이 성공적으로 이루어질 경우에 해당합니다.
Rhythm Pharmaceuticals (RYTM) a reçu la désignation de médicament orphelin du ministère de la Santé du Japon pour le setmelanotide, ciblant le traitement de l'obésité hypothalamique acquise. Le setmelanotide, un agoniste MC4R conçu pour traiter l'hyperphagie et l'obésité, est actuellement évalué dans un essai de Phase 3 à l'échelle mondiale, avec des données préliminaires attendues au deuxième trimestre 2025.
Cette désignation souligne le besoin médical non satisfait important au Japon, où environ 5 000 à 8 000 patients vivent avec une obésité hypothalamique acquise. Cette condition touche environ 5 000 à 10 000 personnes aux États-Unis et 3 500 à 10 000 dans l'UE. Cette maladie rare survient généralement à la suite d'une lésion hypothalamique causée par des tumeurs cérébrales, un traumatisme crânien, un AVC ou une inflammation.
La désignation orpheline tant au Japon qu'en Europe positionne Rhythm pour potentiellement offrir le tout premier traitement ciblant la biologie sous-jacente de l'obésité hypothalamique, sous réserve de résultats favorables de l'essai de Phase 3 et d'approbations réglementaires.
Rhythm Pharmaceuticals (RYTM) hat von Japans Gesundheitsministerium die Orphan-Drug-Designierung für Setmelanotide erhalten, das auf die Behandlung von erworbener hypothalamischer Fettleibigkeit abzielt. Setmelanotide, ein MC4R-Agonist, der zur Behandlung von Hyperphagie und Fettleibigkeit entwickelt wurde, wird derzeit in einer globalen Phase-3-Studie evaluiert, wobei die ersten Ergebnisse im zweiten Quartal 2025 erwartet werden.
Die Designierung hebt den erheblichen ungedeckten medizinischen Bedarf in Japan hervor, wo schätzungsweise 5.000 bis 8.000 Patienten mit erworbener hypothalamischer Fettleibigkeit leben. Die Erkrankung betrifft etwa 5.000-10.000 Menschen in den USA und 3.500-10.000 in der EU. Diese seltene Krankheit tritt typischerweise nach einer hypothalamischen Verletzung durch Hirntumore, traumatische Hirnverletzungen, Schlaganfälle oder Entzündungen auf.
Die Orphan-Designation sowohl in Japan als auch in Europa positioniert Rhythm, um potenziell die erste Behandlung anzubieten, die die zugrunde liegende Biologie der hypothalamischen Fettleibigkeit anspricht, vorausgesetzt, die Ergebnisse der Phase-3-Studie sind erfolgreich und die regulatorischen Genehmigungen werden erteilt.
- Received orphan drug designation in Japan, expanding market potential
- Phase 3 trial progressing with results expected Q2 2025
- Potential first-to-market treatment for hypothalamic obesity
- Significant market opportunity across Japan, U.S., and E.U. with 13,500-28,000 total patients
- Phase 3 trial results still pending - success not guaranteed
- Small patient population may limit revenue potential
- Regulatory approvals still required in all markets
Insights
Rhythm Pharmaceuticals securing orphan drug designation (ODD) for setmelanotide in Japan represents a significant regulatory milestone with positive financial implications. This designation strengthens RYTM's global commercial strategy by potentially providing market exclusivity in Japan - a critical benefit for rare disease therapeutics targeting the estimated 5,000-8,000 Japanese patients with hypothalamic obesity.
The ODD in Japan complements their existing European designation, establishing a consistent global regulatory approach ahead of their anticipated Q2 2025 Phase 3 data readout. From a financial perspective, this designation typically accelerates regulatory review timelines and may reduce development costs through potential subsidies and tax incentives specific to Japan's orphan drug program.
The addressable patient population across Japan, US, and Europe (approximately 13,500-28,000 patients total) represents a focused market opportunity characteristic of rare disease therapeutics, which typically command premium pricing. As the company positions setmelanotide as potentially the first approved therapy specifically targeting hypothalamic obesity's underlying biology, this milestone enhances their competitive positioning and potential revenue generation in the Japanese market.
While commercial success ultimately depends on Phase 3 results, this regulatory achievement demonstrates management's execution on their global strategy and enhances RYTM's potential market reach, providing a more diversified revenue opportunity across multiple key pharmaceutical markets.
The orphan drug designation for setmelanotide in Japan marks important clinical progress for addressing hypothalamic obesity, a condition with no approved targeted therapies. This rare disorder, affecting thousands globally, develops after hypothalamic injury - commonly following brain tumor removal, traumatic injury, stroke, or inflammation.
Setmelanotide's mechanism as a melanocortin-4 receptor agonist directly targets the disrupted hypothalamic pathways that regulate hunger and energy expenditure in these patients. The MC4R pathway is important for appetite regulation, and its dysfunction in hypothalamic injury leads to the hallmark symptoms: hyperphagia (pathological hunger) and rapid weight gain resistant to conventional treatments.
The clinical significance extends beyond weight management - hypothalamic obesity patients experience substantial medical complications and quality-of-life impairments. Current management approaches (dietary, behavioral, and non-specific medications) typically yield inadequate results, highlighting the substantial unmet need acknowledged by Japan's MHLW through this designation.
With Phase 3 data expected next quarter, the scientific community awaits evidence on setmelanotide's efficacy in this specific population. A positive outcome would represent a paradigm shift toward precision medicine in hypothalamic obesity treatment, offering the first therapy specifically addressing the condition's neurobiological underpinnings rather than merely treating symptoms.
BOSTON, March 19, 2025 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced it has received orphan drug designation from Japan’s Ministry of Health, Labour and Welfare (MHLW) for setmelanotide as a treatment for acquired hypothalamic obesity.
Setmelanotide is a melanocortin-4 receptor (MC4R) agonist designed to treat hyperphagia and obesity. Rhythm is evaluating setmelanotide in a global Phase 3 trial in patients with acquired hypothalamic obesity, with topline data on track to be disclosed in the second quarter of 2025.
“Orphan drug designation points to the need for therapeutic options for people living with acquired hypothalamic obesity,” said Yann Mazabraud, Executive Vice President, Head of International at Rhythm Pharmaceuticals. “With this designation now in place in Japan, as well as in Europe, we believe we are well positioned to execute on our global strategy to bring patients with hypothalamic obesity the first-ever treatment targeting the underlying biology of this disease, pending success of our Phase 3 trial and subsequent regulatory filings.”
Acquired hypothalamic obesity is a disease characterized by accelerated and sustained change in weight trajectory caused by an injury to the hypothalamus, often accompanied by hyperphagia (pathological, insatiable hunger and impaired satiety accompanied by abnormal food-seeking behaviors) and/or decreased energy expenditure. Acquired hypothalamic obesity most frequently follows hypothalamic injury from the growth or surgical removal of craniopharyngioma, astrocytoma, or other rare brain tumors. Additional causes of injury may include traumatic brain injury, stroke, or inflammation due to infection.
“There is a significant unmet medical need in Japan for a safe and effective precision medicine for patients living with acquired hypothalamic obesity, said Prof. Arima, MD, PhD, Professor of the Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine. “Setmelanotide could provide new hope to these patients and their families.”
In Japan, drugs can be designated as orphan drugs if they treat diseases affecting fewer than 50,000 patients in Japan and there is a high medical need. Rhythm estimates there are 5,000 to 8,000 people living with acquired hypothalamic obesity in Japan, 5,000 to 10,000 people living with acquired hypothalamic obesity in the U.S., and 3,500 to 10,000 people living with acquired hypothalamic obesity in the E.U.
About Rhythm Pharmaceuticals
Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or genetically confirmed pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), deficiency or leptin receptor (LEPR) deficiency. Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA.
Setmelanotide Indication
In the United States, setmelanotide is indicated to reduce excess body weight and maintain weight reduction long term in adult and pediatric patients aged 2 years and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS) or Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). In the European Union and the United Kingdom, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 2 years of age and above. In the European Union and the United Kingdom, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology.
Limitations of Use
Setmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective:
- Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign
- Other types of obesity not related to BBS or POMC, PCSK1, or LEPR deficiency, including obesity associated with other genetic syndromes and general (polygenic) obesity
Contraindication
Prior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported.
WARNINGS AND PRECAUTIONS
Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.
Depression and Suicidal Ideation: Depression, suicidal ideation and depressed mood have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.
Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue IMCIVREE.
Skin Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic Nevi: Generalized or focal increases in skin pigmentation, darkening of pre-existing nevi, development of new melanocytic nevi and increase in size of existing melanocytic nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new pigmented lesions.
Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol preserved drugs.
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥
USE IN SPECIFIC POPULATIONS
Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.
To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe.
Please see the full Prescribing Information for additional Important Safety Information.
Forward-looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the ability of setmelanotide to treat patients with hypothalamic obesity, our expectations surrounding potential regulatory submissions, progress, or approvals for any of our product candidates, including in the US and Japan, the estimated market size and addressable population for our drug products; the announcement of data from our clinical trials, including our Phase 3 trial evaluating setmelanotide for patients with acquired hypothalamic obesity, and the timing of any of the foregoing. Statements using words such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks, uncertainties and other important factors, including, but not limited, to our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the ability to achieve necessary regulatory approvals, risks associated with data analysis and reporting, failure to identify and develop additional product candidates, unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, risks associated with the laws and regulations governing our international operations and the costs of any related compliance programs, the impact of competition, risks relating to product liability lawsuits, inability to maintain collaborations, or the failure of these collaborations, our reliance on third parties, risks relating to intellectual property, our ability to hire and retain necessary personnel, general economic conditions, risks related to internal control over financial reporting, and the other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise.
Corporate Contact:
David Connolly
Head of Investor Relations and Corporate Communications
Rhythm Pharmaceuticals, Inc.
857-264-4280
dconnolly@rhythmtx.com
Media Contact:
Sheryl Seapy
Real Chemistry
(949) 903-4750
sseapy@realchemistry.com
FAQ
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