bivamelagon (LB54640) / LG Chem, Rhythm Pharma - LARVOL DELTA

A Long-Term Study of Bivamelagon in Participants With Hypothalamic Obesity (HO) (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Rhythm Pharmaceuticals, Inc.

New P2 trial • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Anticipated Upcoming Milestones (GlobeNewswire) - "Complete submissions of a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) and a Type II variation request to the European Medicines Agency seeking approval for setmelanotide for the treatment of acquired hypothalamic obesity in the third quarter of 2025....Announce topline data in the 12-patient Japanese cohort of the setmelanotide Phase 3 trial in acquired hypothalamic obesity in the first quarter of 2026; Announce topline data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first quarter of 2026; Complete enrollment in the setmelanotide Phase 3 trial substudy in congenital hypothalamic obesity in the first half of 2026; and Pending alignment with U.S and European regulatory agencies, initiate a pivotal Phase 3 trial evaluating bivamelagon in acquired hypothalamic obesity in 2026."

Enrollment status • Filing • New P3 trial • P3 data: top line • Hypothalamic Injury-associated Obesity • Obesity

Efficacy and Safety of Once-Daily Oral Bivamelagon in Acquired Hypothalamic Obesity: Results from a Double-blind, Multicenter, Placebo-Controlled, Randomized Phase 2 Trial (Rhythm Press Release) - P2 | N=28 | NCT06046443 | Sponsor: Rhythm Pharmaceuticals, Inc. | "In the 14-week, double-blind, four-arm, placebo-controlled portion of the trial, bivamelagon achieved statistically significant and clinically meaningful reductions in body mass index (BMI), consistent with BMI reductions achieved with setmelanotide therapy in similar patient populations in past trials. Other highlights include: 9.3% BMI reduction from baseline in the 600mg cohort (n=8) (p-value= 0.0004); 7.7% BMI reduction from baseline in the 400mg cohort (n=7) (p-value= 0.0002); 2.7% BMI reduction from baseline in the 200mg cohort (n=6) (p-value= 0.0180); and BMI for patients in the placebo cohort (n=7) increased by 2.2% over 14 weeks."

P2 data • Hypothalamic Injury-associated Obesity • Obesity

Efficacy And Safety Of Once-daily Oral Bivamelagon In Acquired Hypothalamic Obesity: Results From A Double-blind, Multicenter, Placebo-controlled, Randomized Phase 2 Trial (ENDO 2025) - P2 | "The favorable results from the Phase 3 trial of the injectable MC4R agonist setmelanotide suggest that this mechanism of action has therapeutic utility in aHO. At the time of submission, 21 of 28 participants completed the 14-week trial (1 discontinuation), 20 of whom continued to receive treatment in the OLE. Overall, 46.4% were female, mean (SD; range) age at baseline was 25.4 (16.8; 12-68) years, mean (SD) BMI was 38.7 (8.4) kg/m2, and mean (SD) BMI-Z (<18 years) was 3.13 (1.21). The most common etiology of aHO was craniopharyngioma (82.1%), and the mean (SD) time from confirmed hypothalamicinjury to enrollment was 7.0 (5.0) years."

Clinical • Late-breaking abstract • P2 data • Brain Cancer • Cardiovascular • CNS Tumor • Endocrine Disorders • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity • Oncology

Rhythm Pharmaceuticals Announces Oral MC4R Agonist Bivamelagon Achieved Statistically Significant, Clinically Meaningful BMI Reductions in Placebo-controlled Phase 2 Trial in Acquired Hypothalamic Obesity (Rhythm Press Release) - P2 | N=28 | NCT06046443 | Sponsor: Rhythm Pharmaceuticals, Inc. | "In the 14-week, double-blind, four-arm, placebo-controlled portion of the trial, bivamelagon achieved: -9.3% BMI reduction from baseline in the 600mg cohort (n=8) (p-value=0.0004); -7.7% BMI reduction from baseline in the 400mg cohort (n=7) (p-value=0.0002); -2.7% BMI reduction from baseline in the 200mg cohort (n=6) (p-value=0.0180); and BMI for patients in the placebo cohort (n=7) increased by 2.2% over 14 weeks....With these results in hand, Rhythm plans to seek input from U.S. and EU regulatory authorities on a Phase 3 trial design to advance bivamelagon in acquired hypothalamic obesity. The Company plans to request an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) and to seek scientific advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA)."

New P3 trial • P2 data • Hypothalamic Injury-associated Obesity

Rhythm Pharmaceuticals Announces Oral MC4R Agonist Bivamelagon Achieved Statistically Significant, Clinically Meaningful BMI Reductions in Placebo-controlled Phase 2 Trial in Acquired Hypothalamic Obesity (Rhythm Press Release) - "In a post-hoc analysis comparing the randomized Phase 2 results to results from prior setmelanotide trials, bivamelagon demonstrated BMI reductions...In this post-hoc comparison of the subset of setmelanotide patients who demonstrated study compliance and were not on concomitant GLP1 therapy (no patients who enrolled in the Phase 2 bivamelagon trial were on concomitant GLP1 therapy), setmelanotide and bivamelagon achieved: -9.7% and -10.5% mean BMI reductions achieved in a pooled patient population (n=59; n=64) from Phase 2 and Phase 3 trials of setmelanotide therapy at 12 weeks and 16 weeks, respectively; as compared to: -8.8% and -10.1% mean BMI reductions achieved in patients (400mg n=6; 600mg n=7) at 14 weeks of bivamelagon therapy....A total of 27 patients completed the 14-week, placebo-controlled portion of the trial, and 26 of them transitioned into the open-label extension of the trial and remained in that portion of the trial, as of July 7, 2025."

Retrospective data • Trial status • Hypothalamic Injury-associated Obesity • Obesity

Rhythm Pharmaceuticals To Announce Topline Results from Phase 2 Trial Evaluating Oral MC4R Agonist Bivamelagon in Acquired Hypothalamic Obesity (GlobeNewswire) - "Rhythm Pharmaceuticals...announced the Company will hold a conference call and webcast on Wednesday, July 9, 2025 at 8:00 a.m. ET to disclose topline results from the randomized, placebo-controlled portion of the Phase 2 trial evaluating bivamelagon, an investigational oral melanocortin-4 receptor (MC4R) agonist, in patients with acquired hypothalamic obesity....The Phase 2 trial is a randomized, placebo-controlled, double-blind study to assess the effect of bivamelagon (LB54640) on safety, weight reduction, hunger, and quality of life in patients 12 years of age and older (N=28) with hypothalamic obesity."

P2 data • Hypothalamic Injury-associated Obesity

Rhythm Pharmaceuticals Announces Three Late-breaking Data Abstracts Accepted for Presentation at ENDO 2025 (GlobeNewswire) - "Rhythm Pharmaceuticals...today announced that three late-breaking abstracts have been accepted for presentation at The Endocrine Society’s Annual Meeting (ENDO 2025) taking place July 12-15 in San Francisco, CA...In a live oral presentation, Susan Phillips, M.D., Pediatric Endocrinology, University of California San Diego/Rady Children’s Hospital, San Diego, will present data from Rhythm’s pivotal Phase 3 TRANSCEND trial evaluating setmelanotide in the largest randomized, placebo-controlled trial in acquired hypothalamic obesity to date....Vidhu Thaker, M.D., Pediatric Endocrinology, Columbia University, New York City will present a poster from the 14-week, multicenter, international, randomized, double-blind, placebo-controlled Phase 2 trial of bivamelagon, an oral MC4R agonist (formerly LB54640), in participants with acquired hypothalamic obesity."

Clinical data • Obesity

Rhythm Pharmaceuticals Reports First Quarter 2025 Financial Results and Business Update (GlobeNewswire) - "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; Announce topline data from the bivamelagon Phase 2 trial in acquired HO in the third quarter of 2025; Complete enrollment in the setmelanotide Phase 2 trial in PWS in the second half of 2025; Complete enrollment in the Phase 1, Part C trial evaluating the weekly, MC4R agonist RM-718 in patients with acquired HO in the second half of 2025."

EMA filing • FDA filing • P2 data • Trial status • Obesity • Prader–Willi syndrome

A Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

Rhythm Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Business (GlobeNewswire) - "Begin enrolling the first patients with congenital HO in a 34-week substudy of setmelanotide being conducted under the protocol for its global Phase 3 trial in the first quarter of 2025; Begin enrolling the first patients with Prader-Willi syndrome (PWS) in a 26-week, open-label Phase 2 trial evaluating setmelanotide in the first quarter of 2025; Begin enrolling patients with acquired HO in Part C of the Phase 1 trial evaluating the weekly, MC4R agonist RM-718 in the first quarter of 2025; Announce top-line data in the Phase 3 trial evaluating setmelanotide in acquired HO in the second quarter of 2025; Announce topline data from the Phase 2 trial of bivamelagon in acquired HO in the second half of 2025; and Announce top-line data in the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases in the first half of 2026."

Enrollment status • P2 data • P3 data: top line • Hypothalamic Injury-associated Obesity • Metabolic Disorders • Obesity • Prader–Willi syndrome

Rhythm Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Business (GlobeNewswire) - "Today, the Company announced that it raised approximately $75 million in gross proceeds from the sale of approximately 1.3 million shares of common stock...Today, Rhythm announced that it completed enrollment in the Phase 2 trial evaluating oral MC4R agonist bivamelagon (LB54640) in acquired hypothalamic obesity...Net product revenues relating to global sales of IMCIVREE were $41.8 million for the fourth quarter of 2024 and $130.1 million for the full year of 2024..."

Commercial • Enrollment closed • Financing • Metabolic Disorders • Obesity

Rhythm Pharmaceuticals Announces Preliminary Fourth Quarter and Full Year 2024 Net Product Revenues, Pipeline Advancements and Upcoming Milestones (GlobeNewswire) - "Rhythm is on track to complete enrollment in the Phase 2 trial evaluating bivamelagon, an oral MC4R agonist, in acquired HO in the first quarter of 2025...Following acceptance of a protocol amendment, Rhythm expects to begin dosing patients with acquired HO in Part C of the Phase 1 trial evaluating RM-718, a weekly MC4R agonist, in the first quarter of 2025."

Enrollment status • Trial status • Metabolic Disorders • Obesity

A Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

A Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Rhythm Pharmaceuticals, Inc. | Initiation date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Mar 2025 ➔ Jan 2026

Trial initiation date • Trial primary completion date • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity

A Phase 2 Study to Assess Efficacy and Safety of LB54640 in Patients With Genetic Obesity (clinicaltrials.gov) - P2 | N=4 | Not yet recruiting | Sponsor: LG Chem

New P2 trial • Genetic Disorders • Leptin Receptor Deficiency Obesity • Obesity • POMC-null Obesity • PCSK1

A First in Human Study to Assess the Safety, Tolerability of LB54640 in in Healthy Overweight and Obese Subjects (clinicaltrials.gov) - P1 | N=112 | Completed | Sponsor: LG Chem

New P1 trial • Obesity

A Phase 2, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: LG Chem

New P2 trial • Genetic Disorders • Hypothalamic Injury-associated Obesity • Obesity