Rhythm RM-718: -11.6% BMI Drop in Hypothalamic Obesity

Rhythm Pharmaceuticals (RYTM) reported preliminary Phase 2 data for RM-718, its once-weekly MC4R-specific agonist, showing a mean -11.6% BMI reduction from baseline at 16 weeks (n=7) in patients with acquired hypothalamic obesity. Rhythm simultaneously posted Q2 2026 IMCIVREE (setmelanotide) revenue of $71.3 million, up 19% sequentially from the first quarter.

RYTM closed at $105.78 on August 3 with a market cap of approximately $7.05 billion. The stock has rallied roughly 40% over the past three months as the IMCIVREE launch in acquired HO gained traction: the drug generated over 150 patient start forms since its March 2026 FDA approval in the indication.

The MC1R-sparing bet

Setmelanotide, Rhythm’s daily injectable MC4R agonist, is FDA-approved for HO, Bardet-Biedl syndrome, POMC deficiency, and LEPR deficiency. The drug works. The problem is generalized skin hyperpigmentation, which affects roughly 60% to 80% of patients and is often the reason they discontinue treatment.

RM-718 is engineered to spare the MC1 receptor, the pathway responsible for melanin production and the resulting darkening of skin and nevi. The Phase 2 data suggest the design is working: across 11 enrolled patients, only two cases of mild injection-site hyperpigmentation were observed, with zero cases of the generalized darkening that limits setmelanotide adherence.

The -11.6% BMI reduction at 16 weeks is consistent with setmelanotide (-10.1% at 16 weeks across Phase 2 and 3 trials, n=64) and bivamelagon (-10.1% at 14 weeks, 600 mg dose), Rhythm’s oral MC4R agonist. Rhythm plans to enroll 10 to 15 Prader-Willi syndrome patients in the RM-718 study by the end of 2026.

Beat yourself before someone else does

Rhythm is voluntarily developing a replacement for its own flagship product. If RM-718 matches setmelanotide’s efficacy with weekly injection convenience and without the hyperpigmentation liability, it consolidates Rhythm’s hold on the MC4R pathway for rare obesity disorders rather than ceding the next-generation opportunity to a competitor.

The commercial logic is straightforward. IMCIVREE generated $71.3 million in Q2 2026, with US revenue of $51.0 million accounting for 72% of the total. That is roughly $285 million annualized. A next-generation MC4R agonist with better tolerability and weekly dosing could expand the addressable market by converting patients who reject or discontinue setmelanotide because of the skin darkening.

What to watch

The sample is small: n=7 at the 16-week mark in an open-label study. Rare obesity trials have a history of producing BMI reductions that shrink in randomized, placebo-controlled settings. Rhythm has not disclosed a registrational timeline for RM-718, and a Phase 3 program in a disease affecting roughly 5,000 to 10,000 US patients will be slow to enroll.

For investors, the Q2 revenue trajectory is the nearer-term focus. $71.3 million with 19% sequential growth puts IMCIVREE on a path to roughly $300 million annualized, supporting the $7 billion valuation but not justifying a premium without pipeline expansion. RM-718 and bivamelagon together represent Rhythm’s multi-asset bet on owning the MC4R pathway end-to-end.

The guide to reading clinical trial press releases explains what to look for in early-phase readouts like this one. The Rhythm press release provides the full data.