Rhythm Pharmaceuticals Announces Additional Positive Data from Phase 3 TRANSCEND trial of Setmelanotide in Patients with Acquired Hypothalamic Obesity

Rhea-AI Summary

Rhythm Pharmaceuticals (Nasdaq: RYTM) reported additional positive 52-week data from its global Phase 3 TRANSCEND trial of setmelanotide in acquired hypothalamic obesity. Results showed a -18.8% placebo-adjusted BMI reduction (N=142) and mean BMI change of -16.4% on drug versus +2.4% on placebo (p<0.0001).

The dataset adds 12 Japanese patients and 10 supplemental patients. The company set a PDUFA goal date of March 20, 2026 for its supplemental NDA and will submit the final data package to the FDA on March 2, 2026. EMA CHMP opinion is anticipated in Q2 2026.

Positive

• -18.8% placebo-adjusted BMI reduction (N=142) at 52 weeks
• Mean BMI -16.4% on setmelanotide vs +2.4% on placebo (p<0.0001)
• Includes additional 12 Japanese and 10 supplemental patients, expanding global dataset
• Regulatory timeline: PDUFA goal date March 20, 2026; final FDA submission March 2, 2026

Negative

• None.

Key Figures

Placebo-adjusted BMI change: -18.8% Setmelanotide BMI change: -16.4% Placebo BMI change: +2.4% +5 more

8 metrics

Placebo-adjusted BMI change -18.8% BMI reduction at 52 weeks for all TRANSCEND patients (N=142)

Setmelanotide BMI change -16.4% Mean BMI reduction from baseline at 52 weeks (n=94)

Placebo BMI change +2.4% Mean BMI change from baseline at 52 weeks (n=48)

Total patients 142 patients All TRANSCEND patients including 12 Japanese and 10 supplemental

Hunger score change (active) -2.5 points Average weekly reduction in most hunger score, age ≥12 (n=66)

Hunger score change (placebo) -1.3 points Average weekly reduction in most hunger score, age ≥12 (n=32)

P-value (primary endpoint) p<0.0001 BMI reduction primary endpoint at 52 weeks for all patients

PDUFA goal date March 20, 2026 FDA review of sNDA for setmelanotide in acquired hypothalamic obesity

Market Reality Check

Price: $86.29 Vol: Volume 1,315,273 is 72% a...

high vol

$86.29 Last Close

Volume Volume 1,315,273 is 72% above 20-day average of 764,261, indicating elevated trading interest pre-announcement. high

Technical Shares at $92.73 are trading below the 200-day MA of $93.98 and 24.12% below the 52-week high of $122.20.

Peers on Argus

RYTM fell 5.45% with elevated volume while close peers showed mixed, mostly mode...

1 Down

RYTM fell 5.45% with elevated volume while close peers showed mixed, mostly modest moves (e.g., ABVX +1.24%, LEGN -0.99%, NUVL -0.98%). Momentum scans only flagged RNA at -4.61%, suggesting a stock-specific move rather than a sector-wide biotech rotation.

Previous Acquisition,clinical trial Reports

5 past events · Latest: Aug 20 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Aug 20	sNDA acceptance, HO	Positive	+3.0%	FDA sNDA acceptance with Priority Review and EMA validation for HO indication.
Jul 09	Phase 2 HO data	Positive	+36.6%	Bivamelagon Phase 2 trial showed statistically significant, clinically meaningful BMI reductions.
Jul 08	Topline call preview	Positive	+36.6%	Announcement of upcoming Phase 2 bivamelagon topline results webcast for HO trial.
Apr 07	Pivotal Phase 3 HO	Positive	+17.1%	Pivotal TRANSCEND trial met primary endpoint with -19.8% placebo-adjusted BMI reduction.
Apr 06	Phase 3 HO preview	Positive	+17.1%	Scheduling of webcast to present pivotal Phase 3 TRANSCEND topline results in HO.

Pattern Detected

Positive acquired hypothalamic obesity and clinical milestones have historically coincided with strong positive price reactions for RYTM.

Recent Company History

Over the past year, Rhythm has repeatedly reported positive data and regulatory progress in acquired hypothalamic obesity. The pivotal Phase 3 TRANSCEND topline on Apr 7, 2025 and subsequent sNDA acceptance with Priority Review on Aug 20, 2025 each produced double‑digit gains. Positive Phase 2 results for oral MC4R agonist bivamelagon in July 2025 also triggered substantial upside. Today’s announcement extends this storyline with additional 52‑week TRANSCEND data, integrating Japanese and supplemental patients into the efficacy profile.

Historical Comparison

+22.1% avg move · In the past, 5 acquisition/clinical HO updates for RYTM produced an average move of 22.08%, highligh...

acquisition,clinical trial

+22.1%

Average Historical Move acquisition,clinical trial

In the past, 5 acquisition/clinical HO updates for RYTM produced an average move of 22.08%, highlighting that this news type has often been a major trading catalyst.

News flow shows steady progression in acquired hypothalamic obesity: pivotal Phase 3 TRANSCEND success, sNDA acceptance with Priority Review, supportive Phase 2 data for oral bivamelagon, and now expanded 52‑week TRANSCEND data including Japanese and supplemental patients.

Regulatory & Risk Context

Active S-3 Shelf · $200,000,000

Shelf Active

Active S-3 Shelf Registration 2026-02-26

$200,000,000 registered capacity

An effective S-3ASR filed on Feb 26, 2026 registers resale of 2,395,831 common shares issuable upon preferred conversion and establishes an at-the-market offering program for up to $200,000,000 of common stock with TD Securities (USA) LLC, providing pre-cleared capacity for future equity issuance.

Market Pulse Summary

This announcement adds mature 52‑week data from the Phase 3 TRANSCEND trial, showing an -18.8% place...

Analysis

This announcement adds mature 52‑week data from the Phase 3 TRANSCEND trial, showing an -18.8% placebo‑adjusted BMI reduction across 142 patients and significant hunger-score improvements. It reinforces the upcoming March 20, 2026 PDUFA decision and parallel reviews at the EMA and Japan’s PMDA. Investors may track regulatory outcomes, any use of the new $200,000,000 ATM facility, and how these data integrate into broader MC4R-pathway development plans.

Key Terms

phase 3, bmi, pdufa, snda, +4 more

8 terms

phase 3 medical

"announced additional positive data from its global Phase 3 TRANSCEND trial of setmelanotide"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

bmi medical

"-18.8% placebo-adjusted difference1 in BMI reduction (N=142);Primary endpoint of mean BMI reduction"

Body mass index (BMI) is a simple number calculated from a person’s weight and height that classifies them as underweight, normal weight, overweight, or obese; think of it as a quick ratio like miles per gallon for body size. Investors watch BMI because shifts in population averages influence demand for healthcare services, drugs, medical devices, and insurance costs, and they can signal longer-term trends in workforce health and public spending.

pdufa regulatory

"March 20, 2026 PDUFA goal date for sNDA for setmelanotide in acquired hypothalamic obesity"

PDUFA, short for the Prescription Drug User Fee Act, is a law that allows drug companies to pay fees to the government to speed up the review process for new medicines. This helps bring important drugs to market more quickly, which can impact their availability and pricing. For investors, PDUFA timelines can influence the timing of a drug’s approval and potential market success.

snda regulatory

"PDUFA goal date for sNDA for setmelanotide in acquired hypothalamic obesity"

A SNDA (Subordination, Non‑Disturbance and Attornment Agreement) is a legal pact among a property owner’s lender, the owner’s tenants, and sometimes the landlord that sets who keeps lease rights if the property is sold or a mortgage is enforced. Think of it as a rulebook that decides whether a tenant can stay and keep paying rent or must answer to a new owner after a foreclosure. For investors, an SNDA matters because it protects predictable rental income, clarifies who has priority on claims against a property, and therefore affects a property’s value and the security of related loans.

marketing authorization application (maa) regulatory

"Type II variation submission to the Marketing Authorization Application (MAA) for setmelanotide"

A marketing authorization application (MAA) is a formal request submitted to a health regulator asking permission to sell a medicine or medical product in a market. Think of it like applying for a driver's license for a new drug: the regulator checks safety, quality and effectiveness before granting permission. For investors, the MAA stage matters because approval typically unlocks commercial sales and revenue, while rejection or delay creates major value and timing risk.

committee for medicinal products for human use (chmp) regulatory

"The Company anticipates the Committee for Medicinal Products for Human Use (CHMP) would issue an opinion"

The Committee for Medicinal Products for Human Use is the group of scientific experts at the European medicines regulator that assesses whether a medicine is safe, effective and high quality for use in people and issues the regulator’s formal scientific opinion. Investors watch its opinions because they act like a building inspector’s stamp for a drug — a positive opinion clears the path to sales across a large market and reduces regulatory risk, while a negative opinion can block or delay commercial plans.

european medicines agency (ema) regulatory

"The European Medicines Agency (EMA) is reviewing Rhythm’s Type II variation submission"

The European Medicines Agency (EMA) is a public organization responsible for evaluating and supervising medicines used in Europe to ensure they are safe and effective. For investors, the EMA's decisions can influence pharmaceutical companies' success, regulatory approvals, and the availability of new treatments, all of which can impact the value of related stocks and industry trends.

pharmaceuticals and medical devices agency (pmda) regulatory

"The Company will also submit the full data package to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA)"

A national regulatory agency that evaluates, approves and monitors medicines, medical devices and related products for safety, quality and effectiveness, including reviewing clinical data, inspecting manufacturing and tracking post‑market safety. For investors, its decisions act like a gatekeeper’s stamp: approvals clear the path to sales and revenue growth, while delays, rejections or safety warnings can push back launches, raise costs and increase investment risk.

AI-generated analysis. Not financial advice.

-- -18.8% placebo-adjusted difference in BMI reduction achieved in all patients (N=142) at 52 weeks, including 12 Japanese patients and 10 supplemental patients with acquired hypothalamic obesity --

-- March 20, 2026 PDUFA goal date for sNDA for setmelanotide in acquired hypothalamic obesity --

BOSTON, March 01, 2026 (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 additional positive data from its global Phase 3 TRANSCEND trial of setmelanotide in patients with acquired hypothalamic obesity (HO). This new data set includes 12 patients from a Japanese cohort and 10 supplemental patients who were enrolled in addition to the primary 120-patient pivotal cohort.

Highlights from these 52-week data include:

• -18.8% placebo-adjusted difference¹ in BMI reduction (N=142);
• Primary endpoint of mean BMI reduction of -16.4% from baseline for all patients on setmelanotide therapy (n=94) compared with +2.4% BMI change for patients on placebo (n=48) at 52 weeks (95% CI; p<0.0001); and
• Among patients aged 12 and older (n=98), the setmelanotide group (n=66) showed an average weekly reduction of 2.5 points in the weekly average most hunger score, compared with a 1.3‑point reduction in the placebo group (n=32) (p=0.0015).
  
  

“Building off our strong pivotal data, these efficacy data further support setmelanotide’s potential to become the first therapy approved for patients living with the hunger, reduced energy expenditure, accelerated weight gain, and obesity of acquired hypothalamic obesity,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “We look forward to continuing our positive dialogue with regulators, and we are well prepared to bring setmelanotide to patients with acquired HO, pending U.S. Food and Drug Administration (FDA) approval."

Rhythm previously announced the TRANSCEND trial met its primary and key secondary endpoints when it disclosed topline data from the pre-specified 120-patient pivotal cohort in April 2025. The Company’s supplemental New Drug Application (sNDA) is under review by the U.S. Food and Drug Administration (FDA) with a PDUFA goal date of March 20, 2026. Rhythm will submit the final data package to the FDA on March 2, 2026 ahead of the previously agreed upon submission date for the supplemental data.  

The European Medicines Agency (EMA) is reviewing Rhythm’s Type II variation submission to the Marketing Authorization Application (MAA) for setmelanotide for the same indication. The Company anticipates the Committee for Medicinal Products for Human Use (CHMP) would issue an opinion to the European Commission (EC) in the second quarter of 2026 with potential marketing authorization in the second half of 2026. The Company will also submit the full data package to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and plans to seek marketing authorization for setmelanotide to treat acquired hypothalamic obesity there, as well.

About Acquired Hypothalamic Obesity
Acquired hypothalamic obesity is a rare disease characterized by accelerated and sustained weight gain caused by an injury to the hypothalamus. Hypothalamic injury may lead to decreased alpha-melanocyte-stimulating hormone (α-MSH) production and impairment of MC4R pathway signaling. The MC4R pathway is responsible for regulating energy balance and body weight. Acquired hypothalamic obesity most frequently follows the growth or treatment of craniopharyngioma, astrocytoma or other hypothalamic-pituitary tumors. Additional causes of injury may include traumatic brain injury, stroke or inflammation. Due to impairment of the MC4R pathway, patients experience accelerated and sustained weight gain, often accompanied by hyperphagia and/or decreased energy expenditure. Acquired hypothalamic obesity can occur as early as six months following hypothalamic injury. Rhythm estimates 10,000 patients living with acquired HO in the United States, approximately 10,000 patients in Europe and between 5,000 to 8,000 people living with acquired hypothalamic obesity in Japan.

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 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 ≥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 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 our pivotal Phase 3 TRANSCEND study evaluating setmelanotide for the treatment of acquired hypothalamic obesity, including the additional data set of 12 patients from a Japanese cohort and 10 supplemental patients enrolled in addition to the primary 120-patient pivotal cohort; the potential for setmelanotide to treat hypothalamic obesity; the safety, efficacy, potential benefits of, and clinical design or progress of any of our products or product candidates at any dosage or in any indication; our expectations surrounding potential regulatory submissions, progress, or approvals and timing thereof for any of our product candidates, including the sNDA to the FDA and the PDUFA goal date of March 20, 2026, including the submission of the final data package to the FDA, the Type II variation request to the EMA and the anticipated decision by the CHMP to issue an opinion to EC and potential marketing authorization in the second half of 2026; as well as the Company’s engagement with PMDA and plans to seek authorization for setmelanotide to treat acquired hypothalamic obesity in Japan; the estimated market size and addressable population for our drug products, including setmelanotide for the treatment of hypothalamic obesity in the United States, the EU and Japan; and presentation of the full data from the TRANSCEND study at an upcoming medical meeting; including the content, date and 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 those discussed under the caption “Risk Factors” in Rhythm’s Annual Report on Form 10-K for the year ended December 31, 2025, 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:
Layne Cosgrove
Real Chemistry
(410) 916-1035
llitsinger@realchemistry.com

¹ ANCOVA model with unequal variance to account for possible unequal residual variances was used to estimate the difference between treatment groups. Rubin’s Rule was used to provide the overall estimates of differences in least square (LS) means, corresponding CI and p-value.

FAQ

What did Rhythm Pharmaceuticals announce on March 1, 2026 about RYTM setmelanotide?

They announced additional positive 52-week TRANSCEND Phase 3 data showing significant BMI reductions. According to the company, the expanded dataset (N=142) produced a placebo-adjusted BMI reduction of -18.8% and a mean drug BMI change of -16.4% (p<0.0001).

What were the TRANSCEND trial BMI results for RYTM at 52 weeks?

Setmelanotide showed a mean BMI reduction of -16.4% versus +2.4% for placebo at 52 weeks. According to the company, the placebo-adjusted difference was -18.8% (N=142) with statistical significance (p<0.0001).

When is Rhythm’s PDUFA date for the RYTM supplemental NDA for acquired hypothalamic obesity?

The PDUFA goal date is scheduled for March 20, 2026. According to the company, the supplemental NDA is under FDA review and the final data package will be submitted on March 2, 2026 ahead of that date.

How many patients were included in the expanded TRANSCEND dataset for RYTM and where were they enrolled?

The expanded dataset included 142 total patients, adding 12 Japanese10 supplemental

What secondary clinical findings did Rhythm report for setmelanotide in TRANSCEND?

Among patients aged 12+, setmelanotide showed greater hunger score improvement versus placebo (weekly average reduction 2.5 vs 1.3 points). According to the company, this result reached statistical significance (p=0.0015), supporting symptomatic benefit.