Rhythm Pharmaceuticals Announces New Data Presentations on Patients with Acquired or Congenital Hypothalamic Obesity (N=35) Treated with Setmelanotide for up to Nine Months in French Early-access Program
-- New data showed setmelanotide achieved consistent, meaningful weight reduction --
-- Multiple presentations delivered at the first-ever
Physicians from
“These real-world data show that patients with acquired or congenital hypothalamic obesity on setmelanotide treatment achieved clinically meaningful weight reductions and reductions in hunger beginning at three months that were sustained and deepened in those patients who reached six and nine months on therapy,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “There is a significant unmet need for a treatment that can address the weight gain and overwhelming hunger that patients with either acquired or congenital hypothalamic obesity live with, and we believe these data – which are consistent with data from our Phase 2 and 3 clinical trials – are supportive of the potential efficacy MC4R agonists can achieve for these patients.”
Real-world setmelanotide weight outcomes in French patients with acquired or congenital hypothalamic obesity
The presentations delivered at ESPE-ESE and ECO 2025 detailed clinical outcomes from 30 patients (10 patients younger than 18; 20 patients 18 or older) with acquired hypothalamic obesity who received setmelanotide treatment as part of the pre-approval, early-access program at 14 different treatment centers in
- Of the 20 adult patients with acquired hypothalamic obesity treated with setmelanotide therapy:
- Across all patients, there was an overall -11.9% mean change in body mass index (BMI) from baseline at month 3;
- Ten (n=10) who reached month 6 on therapy achieved -19.2% mean change in BMI; and
- Eight (n=8) who reached month 9 on therapy achieved -23.0% mean change in BMI; and
- Adult patients reported meaningful decreases in hunger scores after 3 and 6 months of treatment with setmelanotide.
- For pediatric patients with acquired hypothalamic obesity treated with setmelanotide, BMI z-score (a measure that represents standard deviations of a child’s BMI that corrects for age and sex) decreased from baseline at all timepoints analysed. A clinically meaningful reduction in BMI z-score is defined as a ≥0.2-point reduction. Data from these pediatric patients include:
- Ten (n=10) pediatric patients who reached month 3 on therapy achieved a mean BMI z-score decrease of 0.3 from baseline;
- Seven (n=7) pediatric patients who reached month 6 on therapy achieved a mean BMI z-score decrease of 0.4 decrease from baseline; and
- Two (n=2) pediatric patients who reached month 9 on therapy achieved a mean BMI z-score decrease of 0.4 from baseline.
The presentation at ECO 2025 also featured data from five patients (4 younger than 18; 1 older than 18) with congenital hypothalamic obesity. Highlights include:
- Four (n=4) pediatric patients who reached month 3 on setmelanotide therapy achieved a mean BMI z-score decrease of -0.2 from baseline; and
- Three (n=3) pediatric patients who reached month 6 on setmelanotide therapy achieved a mean BMI z-score decrease of -0.4 from baseline; and
- One adult patient with congenital hypothalamic obesity achieved a -14.8% BMI reduction baseline at month 6 of setmelanotide therapy.
Setmelanotide was generally well tolerated with the most frequent AEs being injection site reactions and skin hyperpigmentation. No new safety signals related to use of setmelanotide were observed, consistent with setmelanotide’s well-established and well-understood safety profile. For further information about setmelanotide’s safety profile, please see the information below under “WARNINGS AND PRECAUTIONS”.
Additional Congress Presentations
Additional Rhythm presentations were also shared at ECO and ESPE/ESE. Two presentations will also be shared at the
ECO 2025
Rhythm and its collaborators also presented one encore oral presentation, three encore poster presentations and hosted one satellite symposium at ECO:
- “DAYBREAK Trial: Setmelanotide vs placebo in patients with Melanocortin-4 Receptor Pathway Variants”
- “Frequency of Bardet-Biedl syndrome variants in a population with early-onset obesity”
- “Weight loss at 18 months of setmelanotide in 2 to <6-year-old patients with rare MC4R pathway diseases”
- “Body composition improvements with 12 months of setmelanotide in acquired hypothalamic obesity”
ESPE-ESE 2025
In addition to sharing the acquired hypothalamic obesity data from the French early-access program, Rhythm and its collaborators also presented two poster presentations and two oral presentations and hosted a satellite symposium at the conference.
- “Setmelanotide treatment in individuals with obesity and PHIP variants: Results from the DAYBREAK trial”
- “Patient and caregiver experiences with setmelanotide treatment in Bardet-Biedl syndrome – real-world evidence and a patient support program”
- “Age of onset of hyperphagia and/or obesity as key predictors of a positive genetic test for POMC, PCSK1 or LEPR deficiency or BBS”
- “Weight loss at 18 months of setmelanotide in 2 to <6-year-old patients with rare MC4R pathway diseases”
PES 2025
Rhythm and its collaborators will present two posters at the 2025
- “Impact of setmelanotide on metabolic syndrome risk score in pediatric patients with acquired hypothalamic obesity”
- “Clinical characteristics of 2 to 5-year-old patients with hyperphagia and obesity secondary to melanocortin-4 receptor pathway diseases and 1-year response to setmelanotide”
All of the Rhythm-related presentations from ECO, ESPE-ECE, and PES are available here: https://hcp.rhythmtx.com/publications-presentations/. These presentations are intended for
Rhythm previously announced that its pivotal Phase 3 trial evaluating setmelanotide for the treatment of acquired hypothalamic obesity met its primary endpoint with a -19.8% placebo-adjusted BMI reduction in 120 patients. The Company remains on track to submit a supplemental New Drug Application to the FDA and a Type II variation request to the European Medicines Agency for setmelanotide for the treatment of patients with acquired HO in the third quarter of 2025. In addition, Rhythm anticipates it will complete enrollment in the Phase 3 trial substudy investigating the use of setmelanotide in congenital hypothalamic obesity in the second half of 2025.
About
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
Setmelanotide Indication
In
In the
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
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 ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
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
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 safety, efficacy, potential benefits of, and regulatory and clinical progress, potential regulatory submissions, approvals and timing thereof of setmelanotide and other product candidates; the clinical design or progress of any of our products or product candidates at any dosage or in any indication, the planned substudy to evaluate patients with congenital hypothalamic obesity and the timing of enrollment for the substudy to our Phase 3 trial evaluating setmelanotide in patients with acquired hypothalamic obesity; 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; our participation in upcoming events and presentations, and the date, time and 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, 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, including those discussed under the caption “Risk Factors” in Rhythm’s Quarterly Report on Form 10-Q for the three months ended
Corporate Contact:
Head of Investor Relations and Corporate Communications
857-264-4280
dconnolly@rhythmtx.com
Media Contact:
Real Chemistry
(949) 903-4750
sseapy@realchemistry.com
Source: Rhythm Pharmaceuticals, Inc.