Rhythm Pharmaceuticals Announces Topline Results from Phase 3 TRANSCEND Trial

Rhythm Pharmaceuticals announced positive topline results from its Phase 3 TRANSCEND trial evaluating setmelanotide in patients with acquired hypothalamic obesity.

The trial met its primary endpoint, showing a statistically significant and clinically meaningful reduction in body mass index (BMI) with setmelanotide versus placebo across both adult and pediatric groups. Patients receiving setmelanotide achieved a mean BMI reduction of 16.5% at 52 weeks, compared to a 3.3% increase in the placebo group (p<0.0001), representing a placebo-adjusted difference of -19.8%.

Among patients 18 and older, BMI dropped by an average of 16.8% on setmelanotide (vs. a 2.4% increase with placebo), while patients under 18 saw a 16.3% reduction (vs. 3.9% increase with placebo).

Additionally:
- 80% of patients achieved at least 5% BMI reduction
- 63% achieved ≥10% reduction
- 51% achieved ≥15% reduction
- 43% achieved ≥20% reduction

Secondary endpoints also showed significant improvements, including reduced hunger scores and positive BMI Z score changes in younger patients. Setmelanotide was generally well tolerated, with the most common side effects being nausea, vomiting, headache, diarrhea, injection site reactions, and skin hyperpigmentation. One treatment-related serious adverse event and one death were reported.

Rhythm also stated it expects its current cash, cash equivalents, and short-term investments will fund operations into 2027.

Rhythm Pharmaceuticals Announces Topline Results from Phase 3 TRANSCEND Trial

Rhythm Pharmaceuticals announced positive topline results from its Phase 3 TRANSCEND trial evaluating setmelanotide in patients with acquired hypothalamic obesity.

The trial met its primary endpoint, showing a statistically significant and clinically meaningful reduction in body mass index (BMI) with setmelanotide versus placebo across both adult and pediatric groups. Patients receiving setmelanotide achieved a mean BMI reduction of 16.5% at 52 weeks, compared to a 3.3% increase in the placebo group (p<0.0001), representing a placebo-adjusted difference of -19.8%.

Among patients 18 and older, BMI dropped by an average of 16.8% on setmelanotide (vs. a 2.4% increase with placebo), while patients under 18 saw a 16.3% reduction (vs. 3.9% increase with placebo).

Additionally:
- 80% of patients achieved at least 5% BMI reduction
- 63% achieved ≥10% reduction
- 51% achieved ≥15% reduction
- 43% achieved ≥20% reduction

Secondary endpoints also showed significant improvements, including reduced hunger scores and positive BMI Z score changes in younger patients. Setmelanotide was generally well tolerated, with the most common side effects being nausea, vomiting, headache, diarrhea, injection site reactions, and skin hyperpigmentation. One treatment-related serious adverse event and one death were reported.

Rhythm also stated it expects its current cash, cash equivalents, and short-term investments will fund operations into 2027.

Rhythm Pharmaceuticals Terminates License and Share Purchase Agreements with RareStone

Boston, MA – March 20, 2025 – Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM) announced it has terminated its Exclusive License and Share Purchase Agreements with RareStone Group Ltd. and RareStone Medicine (Shenzhen) Co., Ltd. Under the termination deal, Rhythm will repay $6.3 million to RareStone and return all previously acquired shares at no additional cost. All rights and obligations under the original agreements are fully discharged, and both parties have mutually released each other from any future claims.

Rhythm Pharmaceuticals, Inc. announced that its 2025 annual meeting of stockholders will be held on June 24, 2025. Stockholders seeking to bring business before the meeting or nominate a director must submit their proposals by March 26, 2025. Proposals intended for inclusion in the company’s proxy statement must also be received by that date.

All submissions must comply with the company’s amended and restated bylaws, SEC regulations, and other applicable laws. Notices should be directed to the company’s Secretary at its Boston headquarters.

Rhythm Pharmaceuticals reported strong financial and operational performance for the fourth quarter and full year 2024, with $41.8 million in revenue from IMCIVREE® (setmelanotide) sales, a 26% sequential increase, primarily driven by Bardet-Biedl syndrome (BBS) treatment. The company also raised $75 million through its ATM equity offering, extending its cash runway into 2027.

Rhythm remains on track to report topline data from its Phase 3 trial evaluating setmelanotide for acquired hypothalamic obesity (HO) in Q2 2025. Enrollment was completed for its Phase 2 trial of oral MC4R agonist bivamelagon and a supplemental 12-patient Japanese cohort for the global Phase 3 trial. The FDA expanded IMCIVREE’s label to include children as young as 2 years old, and the UK’s MHRA extended its marketing authorization for broader indications.

Key upcoming milestones include starting enrollment in trials for congenital HO, Prader-Willi syndrome, and the weekly MC4R agonist RM-718, along with multiple data readouts in 2025 and 2026. The company reported a net loss of $44.6 million for Q4 2024 and $264.6 million for the full year, reflecting increased R&D and SG&A expenses.

Rhythm expects 2025 non-GAAP operating expenses between $285 million and $315 million, excluding stock-based compensation. The company believes its current cash reserves will support operations through 2027.