Rhythm Pharmaceuticals Announces Five Presentations at ESPE 2024, including New Real-world Data in Pediatric Patients with Acquired or Congenital Hypothalamic Obesity Treated with Setmelanotide
Rhythm Pharmaceuticals (NASDAQ: RYTM) presented new real-world data at ESPE 2024 showing positive results from setmelanotide treatment in pediatric patients with hypothalamic obesity. Four pediatric patients achieved >5% weight reduction at three months, with weight decreases ranging from 5.2% to 9.6%. The patients included two cases each of acquired and congenital hypothalamic obesity, treated under France's early-access program. All patients remain on therapy with no new safety signals observed.
The company also announced plans for a new 34-week substudy to evaluate setmelanotide in 39 patients with congenital hypothalamic obesity, with first patient enrollment expected in Q1 2025. Rhythm maintains its timeline for topline data from its pivotal Phase 3 trial in acquired hypothalamic obesity in H1 2025.
Rhythm Pharmaceuticals (NASDAQ: RYTM) ha presentato nuovi dati reali all'ESPE 2024, mostrando risultati positivi dal trattamento con setmelanotide in pazienti pediatrici con obesità ipotalamica. Quattro pazienti pediatrici hanno raggiunto una riduzione del peso superiore al 5% dopo tre mesi, con cali di peso compresi tra il 5.2% e il 9.6%. I pazienti includevano due casi di obesità ipotalamica acquisita e due di obesità ipotalamica congenita, trattati nell'ambito del programma di accesso anticipato francese. Tutti i pazienti continuano la terapia senza nuovi segnali di sicurezza osservati.
L'azienda ha anche annunciato piani per un nuovo sottostudio di 34 settimane per valutare il setmelanotide in 39 pazienti con obesità ipotalamica congenita, con l'arruolamento del primo paziente previsto nel primo trimestre del 2025. Rhythm mantiene la sua tempistica per i dati principali del suo trial di fase 3 fondamentale sull'obesità ipotalamica acquisita nel primo semestre del 2025.
Rhythm Pharmaceuticals (NASDAQ: RYTM) presentó nuevos datos de la vida real en el ESPE 2024 mostrando resultados positivos del tratamiento con setmelanotide en pacientes pediátricos con obesidad hipotalámica. Cuatro pacientes pediátricos lograron una reducción de peso superior al 5% en tres meses, con disminuciones de peso que varían entre el 5.2% y el 9.6%. Los pacientes incluyeron dos casos de obesidad hipotalámica adquirida y dos de obesidad hipotalámica congénita, tratados bajo el programa de acceso anticipado de Francia. Todos los pacientes permanecen en terapia sin nuevos signos de seguridad observados.
La compañía también anunció planes para un nuevo subestudio de 34 semanas para evaluar el setmelanotide en 39 pacientes con obesidad hipotalámica congénita, con la primera inscripción de pacientes esperada en el primer trimestre de 2025. Rhythm mantiene su cronograma para los datos preliminares de su ensayo pivotal de fase 3 en obesidad hipotalámica adquirida en el primer semestre de 2025.
리듬 제약 (NASDAQ: RYTM)은 ESPE 2024에서 소아 환자의 시상하부 비만 치료에 대한 세트멜라노타이드의 긍정적인 결과를 보여주는 새로운 실제 데이터를 발표했습니다. 네 명의 소아 환자가 3개월 내에 5% 이상의 체중 감소를 달성했으며, 체중 감소는 5.2%에서 9.6%까지 다양합니다. 환자들은 각각 두 건의 후천적 및 선천적 시상하부 비만 사례로, 프랑스의 조기 접근 프로그램에 따라 치료받았습니다. 모든 환자는 새로운 안전 신호를 관찰하지 않고 치료를 지속하고 있습니다.
회사는 39명의 선천적 시상하부 비만 환자에 대한 세트멜라노타이드 평가를 위한 새로운 34주 하위 연구 계획도 발표했으며, 첫 환자 등록은 2025년 1분기에 예상됩니다. 리듬 제약은 2025년 상반기에 발견될 후천적 시상하부 비만에 대한 중요한 3상 시험에서 주요 데이터를 위한 일정을 유지합니다.
Rhythm Pharmaceuticals (NASDAQ: RYTM) a présenté de nouvelles données du monde réel lors de l'ESPE 2024, montrant des résultats positifs du traitement par le setmelanotide chez des patients pédiatriques atteints d'obésité hypothalamique. Quatre patients pédiatriques ont obtenu une réduction de poids supérieure à 5 % après trois mois, avec des diminutions de poids allant de 5,2 % à 9,6 %. Les patients comprenaient deux cas d'obésité hypothalamique acquise et congénitale, traités dans le cadre du programme d'accès précoce en France. Tous les patients poursuivent leur traitement sans nouveaux signaux de sécurité observés.
L'entreprise a également annoncé des plans pour une nouvelle étude subsidiaire de 34 semaines afin d'évaluer le setmelanotide chez 39 patients atteints d'obésité hypothalamique congénitale, avec l'inscription du premier patient prévue au premier trimestre 2025. Rhythm maintient son calendrier pour les données préliminaires de son essai pivot de phase 3 sur l'obésité hypothalamique acquise au premier semestre 2025.
Rhythm Pharmaceuticals (NASDAQ: RYTM) hat auf der ESPE 2024 neue reale Daten präsentiert, die positive Ergebnisse der Behandlung mit Setmelanotide bei pädiatrischen Patienten mit hypothalamischer Adipositas zeigen. Vier pädiatrische Patienten erreichten eine Gewichtsreduktion von über 5 % in drei Monaten, mit Gewichtsverlusten zwischen 5,2 % und 9,6 %. Zu den Patienten gehörten jeweils zwei Fälle von erworbener und kongenitaler hypothalamischer Adipositas, die im Rahmen des französischen Frühzugangsprogramms behandelt wurden. Alle Patienten setzen die Therapie fort, ohne dass neue Sicherheitsagenten beobachtet wurden.
Das Unternehmen kündigte zudem Pläne für eine neue 34-wöchige Substudie an, um Setmelanotide bei 39 Patienten mit kongenitaler hypothalamischer Adipositas zu bewerten, wobei die Einschreibung des ersten Patienten für das erste Quartal 2025 erwartet wird. Rhythm hält an seinem Zeitplan für die Hauptdaten seiner entscheidenden Phase-3-Studie zur erworbenen hypothalamischen Adipositas im ersten Halbjahr 2025 fest.
- All four pediatric patients achieved significant weight reduction (5.2-9.6%) after three months of treatment
- One patient showed continued improvement with 9.5% weight reduction at six months
- All patients remain on therapy with no new safety signals observed
- Expansion of clinical program with new 34-week substudy for congenital hypothalamic obesity
- Small sample size of only four patients in the real-world data presentation
- duration of follow-up data (primarily 3 months)
Insights
The real-world data from the French early-access program demonstrates promising clinical outcomes for setmelanotide in both acquired and congenital hypothalamic obesity. The 5-9.6% weight reduction achieved across all four pediatric patients within three months is clinically meaningful, particularly given the treatment-resistant nature of these conditions.
The planned 34-week substudy for congenital hypothalamic obesity represents a strategic expansion of Rhythm's clinical program. With 39 patients targeted for enrollment starting Q1 2025, this complements the ongoing Phase 3 trial in acquired hypothalamic obesity, potentially broadening setmelanotide's market opportunity.
The consistent BMI Z-score improvements and continued patient retention suggest durable treatment effects. This early evidence of efficacy in congenital cases could significantly expand setmelanotide's addressable market beyond its current indications.
-- Four Pediatric patients treated in French early-access program achieved meaningful weight reduction at three months on setmelanotide therapy --
-- Rhythm announced plans for a new substudy to evaluate setmelanotide therapy in patients with congenital hypothalamic obesity --
BOSTON, Nov. 18, 2024 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients living with rare neuroendocrine diseases, today announced the presentation of new, real-world data that showed four pediatric patients with acquired hypothalamic obesity or congenital hypothalamic obesity achieved >
“Patients living with hypothalamic obesity – whether acquired or congenital –are mostly refractory to lifestyle programs and anti-obesity medicines that do not address the underlying cause,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “Based on these case reports and insight generated through our pre-approval early-access program for setmelanotide in France, we look forward to exploring the potential efficacy of setmelanotide to offer a new therapy for these patients.”
3-month real-world setmelanotide hunger and weight outcomes in four French pediatric patients with acquired or congenital hypothalamic obesity
The presentation includes results from four case reports of patients <18 years old, two with acquired hypothalamic obesity and two with congenital hypothalamic obesity, at month three on setmelanotide therapy:
- Congenital hypothalamic obesity:
- Female, age 15, with septo-optic dysplasia as cause of hypothalamic obesity, achieved a body weight decrease of
9.6% from baseline (94 kg) at month 3 and BMI-Z score change from 3.1 at baseline to 2.8; - Male, age 9, with pituitary stalk interruption syndrome (PSIS) as cause of hypothalamic obesity, achieved a body weight decrease of
5.2% from baseline (64 kg) at month 3 and BMI-Z score change from 3.7 at baseline to 3.5;
- Female, age 15, with septo-optic dysplasia as cause of hypothalamic obesity, achieved a body weight decrease of
- Acquired hypothalamic obesity:
- Male, age 13, with acquired hypothalamic obesity related to craniopharyngioma resected at age 9, achieved a body weight decrease of
5.6% from baseline (116 kg) at month 3 and9.5% weight reduction at month 6, and BMI-Z score change from 3.7 at baseline to 3.4 at month six of setmelanotide therapy; and - Male, age 13, with acquired hypothalamic obesity related to radiotherapy for juvenile pilocytic astrocytoma, achieved a body weight decrease of
8.3% from baseline (88.3 kg) at month 3 and BMI-Z score change from 3.1 at baseline to 2.8.
- Male, age 13, with acquired hypothalamic obesity related to craniopharyngioma resected at age 9, achieved a body weight decrease of
These patients were treated with setmelanotide at four different hospitals in France under a pre-marketing, early-access authorization program. All four patients remain on therapy, as of November 15, 2024, and there were no new safety signals observed.
“These patients present with differences and complexities associated with hypothalamic obesity, but these conditions share the same disrupted MC4R pathway signaling,” said Dr. Ahlam Azar-Kolakez, MD, Endocrinology-Diabetology Department, Reference Center for Endocrine Growth and Developmental Diseases, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, France. “These real-world results are the first reported evidence of setmelanotide treatment for patients with congenital hypothalamic obesity demonstrating that it may be an effective, targeted therapy for both acquired and congenital hypothalamic obesity despite differences in etiology.”
Also today, Rhythm announced plans for a new, 34-week substudy designed to evaluate setmelanotide in 39 patients with congenital hypothalamic obesity aged 4 years and older. Rhythm is seeking approval from the U.S. Food and Drug Administration (FDA) for the independent substudy for congenital hypothalamic obesity as a protocol amendment to the Company’s ongoing Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity. Rhythm anticipates enrolling the first patients with congenital hypothalamic obesity in the first quarter of 2025.
The substudy in congenital hypothalamic obesity is independent from Rhythm’s pivotal Phase 3 trial in acquired hypothalamic obesity. The Company remains on track to disclose topline data from that pivotal trial in the first half of 2025.
About Congenital Hypothalamic Obesity
Congenital hypothalamic obesity is a rare disease caused by certain inborn brain abnormalities that may impair the function of the MC4R pathway, which regulates satiety or food intake and energy expenditure. The hallmark features of this disease include hyperphagia and early-onset, refractory obesity that is often linked to an impairment in the MC4R pathway associated with several pituitary deficiencies. Rare diseases that may cause congenital hypothalamic obesity include septo-optic displasia (or de Morsier syndrome), optic nerve hypoplasia, multiple pituitary hormone deficiency (also known as combined pituitary hormone deficiency) and pituitary stalk interruption syndrome. Each of these diseases is considered rare, and between
Additional Presentations at ESPE 2024
In a poster entitled, “Evaluating Setmelanotide Treatment for 12 Months in Pediatric Age Groups With Rare Melanocortin-4 Receptor Pathway–Related Obesity: Efficacy in Weight Reduction and Safety Outcomes,” presenters highlighted the importance of early intervention in young patients with rare MC4R pathway diseases. A cross-sectional analysis of 50 patients aged 2 to 17 years with rare MC4R pathway diseases who participated in one of five different clinical trials of setmelanotide was presented showing that patients regardless of age achieved clinically meaningful weight reductions, and that children between 2 and 5 years old achieved a greater absolute BMI Z reduction.
Additionally, the Company delivered three oral presentations based on analyses of more than 5,000 sequencing samples from the Company’s European genetic testing program for individuals with suspected rare MC4R pathway diseases, Rare Obesity Advanced Diagnosis or ROAD®. Genetic testing of individuals with early-onset obesity can help improve disease etiology understanding and identify patients who may benefit from specialized care.
Highlights from these three presentations included:
1.74% of individuals tested carried a biallelic variant in one of 22 tested genes related to Bardet-Biedl syndrome (BBS), and the frequency in Turkey was5.82% , potentially due to consanguinity rates;22.5% of tested individuals with early-onset obesity carried a variant classified as pathogenic, likely pathogenic or of unknown significance (VUS) of one or more genes closely associated with MC4R pathway function: SIM1, SEMA3 family, PLXNA family, POMC, PCSK1, LEPR, SH2B1 and NCOA1; and4.9% of tested individuals carried a biallelic or heterozygous pathogenic, likely pathogenic or VUS variant in one or more of these genes: ALMS1, BBS, MAGEL2, PHIP, or TBX3 genes. These genes are associated with certain debilitating syndromes.
All of the Rhythm-related presentations from ESPE 2024 are available here: https://hcp.rhythmtx.com/publications-presentations/.
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) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). 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 6 years of age and above. The EC has also authorized setmelanotide for control of hunger and treatment of obesity in children as young as 2 years old, living with BBS or POMC, PCSK1, or LEPR deficiency. 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 for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or 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) or BBS.
In the European Union, 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 Europe, 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 POMC, PCSK1 or LEPR deficiency, or BBS, 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
Skin Pigmentation and Darkening of Pre-Existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred because of its pharmacologic effect. Full body skin examinations prior to initiation and periodically during treatment should be conducted to monitor pre-existing and new pigmentary lesions.
Heart rate and blood pressure monitoring: In Europe, heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide.
Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Patients who have an erection lasting longer than 4 hours should seek emergency medical attention.
Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Patients should be monitored for new onset or worsening depression or suicidal thoughts or behaviors. Consideration should be given to discontinuing setmelanotide 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 setmelanotide.
Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. In Europe, the prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves.
Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: Setmelanotide 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
Lactation: Not recommended when breastfeeding.
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 U.S. Prescribing Information and EU Summary of Product Characteristics 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 potential, safety, efficacy, and regulatory and clinical progress, potential regulatory submissions, approvals and timing thereof of setmelanotide and other product candidates; the timing of results from our global Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity; the planned new substudy to the ongoing Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity that would add and evaluate patients with congenital hypothalamic obesity and the timing of enrollment for the substudy; the potential benefits of any of the Company’s products or product candidates for any specific disease indication or at any dosage, including the potential benefits of setmelanotide for patients with acquired hypothalamic obesity or congenital hypothalamic obesity, POMC, PCSK1, or LEPR variants or genetically confirmed Bardet-Biedl syndrome (BBS); expectations surrounding potential clinical trial results, regulatory submissions and approvals; our participation in upcoming events and presentations, the content thereof 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 and uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in Rhythm’s Quarterly Report on Form 10-Q for the three months ended September 30, 2024 and 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
What were the weight reduction results for RYTM's setmelanotide in pediatric patients?
When will Rhythm Pharmaceuticals (RYTM) begin its new substudy for congenital hypothalamic obesity?
When will RYTM release topline data from its Phase 3 trial in acquired hypothalamic obesity?
