Rhythm Pharmaceuticals Announces FDA Extension of Review Period for IMCIVREE® (setmelanotide) for Patients with Acquired Hypothalamic Obesity

Rhea-AI Summary

Rhythm Pharmaceuticals (NASDAQ: RYTM) said the FDA extended the PDUFA goal date for the sNDA for IMCIVREE (setmelanotide) for acquired hypothalamic obesity from Dec 20, 2025 to Mar 20, 2026.

The FDA requested additional sensitivity analyses of Phase 3 efficacy data; no new data were requested and the amendment did not include safety or manufacturing information. Rhythm said it continues to collaborate with the FDA and is preparing for potential patient access.

The company will host a live conference call and webcast on Nov 7, 2025 at 8:00 a.m. ET; an archived webcast will be available about two hours after the call for 30 days.

Positive

• PDUFA date explicitly set to March 20, 2026
• FDA did not request new data for the sNDA
• Major amendment limited to sensitivity analyses, not safety/manufacturing

Negative

• Regulatory review delayed by ~3 months from Dec 20, 2025
• FDA requested additional sensitivity analyses, extending review workload

Insights

Regulatory affairs analyst

FDA extended the PDUFA date to March 20, 2026 after requesting sensitivity analyses; no new data or safety/manufacturing issues were requested.

Rhythm Pharmaceuticals faces a procedural delay: the FDA labeled additional sensitivity analyses a "major amendment," which extends review by three months from December 20, 2025 to March 20, 2026. The agency did not request new clinical data and specifically excluded safety and manufacturing questions, so the extension stems from analytic follow-up rather than fresh evidence gaps.

This update changes the timeline but does not alter the disclosed evidence set. Key dependencies include the content and completeness of the sensitivity analyses and the FDA’s subsequent assessment; those items will determine whether the application proceeds to approval. Watch for the FDA's written communication on the analyses and any further major amendments over the next three months; expect a definitive regulatory decision or next procedural step by March 20, 2026.

-- FDA sets updated PDUFA goal date of March 20, 2026 – 

-- Company to hold conference today at 8:00 a.m. --

BOSTON, Nov. 07, 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 that the U.S. Food and Drug Administration (FDA) has extended by three months the review period for the supplemental New Drug Application (sNDA) for IMCIVREE^® (setmelanotide) for the treatment of acquired hypothalamic obesity. On Nov. 6, the FDA notified the Company that the Prescription Drug User Fee Act (PDUFA) goal date has been extended from December 20, 2025 to March 20, 2026.

The FDA in October requested additional sensitivity analyses of clinical efficacy data from Rhythm’s Phase 3 pivotal trial in acquired hypothalamic obesity. No new data were requested. The additional information has been deemed a ‘major amendment,’ which allows for additional time for the FDA to review. The major amendment did not include any information relating to the safety or manufacturing of setmelanotide.

“Setmelanotide has demonstrated a compelling product profile, and we have every confidence that these additional sensitivity analyses confirm the strength of the data and setmelanotide’s potential to benefit patients with hypothalamic obesity,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “We appreciate and continue to collaborate with the FDA review team and we also are continuing to advance our preparations to deliver setmelanotide to a patient community that currently has no treatment options approved for acquired hypothalamic obesity.”

Conference Call Information
Rhythm Pharmaceuticals will host a live conference call and webcast at 8:00 a.m. ET today to discuss this update. Participants may register for the conference call here. It is recommended that participants join the call ten minutes prior to the scheduled start.

A webcast of the call will also be available under "Events and Presentations" in the Investor Relations section of the Rhythm Pharmaceuticals website at https://ir.rhythmtx.com/. The archived webcast will be available on Rhythm Pharmaceuticals’ website approximately two hours after the conference call and will be available for 30 days following the call.

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 bivamelagon 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 2 years of age and older with syndromic or monogenic obesity due to Bardet-Biedl syndrome (BBS), 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).

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 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 Hyperpigmentation, Darkening of Pre-existing Nevi, and Development of New Melanocytic 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.

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 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 ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

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 of setmelanotide and other product candidates, including in relation to the PDUFA goal date for the sNDA for setmelanotide in 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 BBS or POMC, PCSK1, or LEPR deficiency; expectations surrounding pending and potential regulatory submissions and approvals, including within the United States, the EU and other regions; business strategy and plans, including regarding commercialization of setmelanotide in the United States, the EU and other regions; 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, 2025 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:
Layne Litsinger
Real Chemistry
(410) 916-1035
llitsinger@realchemistry.com

FAQ

What is the new PDUFA date for Rhythm Pharmaceuticals' IMCIVREE (RYTM)?

The FDA extended the PDUFA goal date to March 20, 2026 (previously Dec 20, 2025).

Why did the FDA extend review of the IMCIVREE sNDA for RYTM?

The FDA deemed additional sensitivity analyses a major amendment, requiring extra review time.

Did the FDA request new clinical or safety data for IMCIVREE (RYTM)?

No; the FDA requested additional sensitivity analyses only and did not request new data.

When is Rhythm Pharmaceuticals' conference call about the FDA update (RYTM)?

Rhythm will host a live conference call and webcast on Nov 7, 2025 at 8:00 a.m. ET.

How long will the archived webcast of Rhythm's RYTM call be available?

The archived webcast will be available approximately two hours after the call and for 30 days.