Stifel analysts were bullish on the data, which showed a 16.5% drop in body-mass index among patients with damage to the hypothalamus taking Rhythm Pharmaceuticals’ Imcivree.
Rhythm Pharmaceuticals’ MC4R agonist Imcivree helped patients with obesity related to brain damage lose weight, teeing up the drug for a label expansion in the burgeoning obesity market, where it already has a handful of approvals.
Data from the Boston-based company’s Phase III trial, called TRANSCEND, was announced Monday. The topline data showed that the trial met its primary endpoint in patients with hypothalamic obesity, eliciting a mean body-mass index (BMI) drop of 16.5% from baseline compared to a 3.3% increase for patients on placebo.
“[W]e believe efficacy here (~20% placebo-adjusted BMI reduction) is outstanding in a highly difficult-to-treat patient population,” Stifel analysts wrote in a note to investors Monday morning. “Moreover, while we had thought much of the discussion around the Wall Street efficacy ‘bar’ was overdone, ‘20%’ here (-17% drug, +3% placebo) is above expectations, and in any normal market/trading environment (we realize the past week is anything but) we’d expect RYTM shares to trade considerably higher.”
Rhythm’s shares rose 2.5% to $48.10 in premarket trading Monday.
The company reported “no new safety signals,” in line with Imcivree’s previously established safety profile. Side effects include mood disruptions like aggression, depression, fatigue, suicidal ideation and trouble sleeping.
Rhythm will use these data for a New Drug Application to the FDA and a Type II variation request to the European Medicines Agency by the third quarter of 2025.
“These planned submissions could pave the way for [Imcivree] to become the first-ever approved therapy for these patients,” Rhythm president and CEO David Meeker said in the company’s statement. “In addition, these strong results with an MC4R agonist increase our confidence in the development of our next-generation MC4R agonists, currently in ongoing Phase 1/2 clinical trials in acquired hypothalamic obesity.”
A fuller readout is coming at an upcoming medical meeting, according to Rhythm. A supplemental trial of 12 patients in Japan is still ongoing, with data from that group coming in the first quarter of 2026, per the company’s statement.
Hypothalamic obesity can result from damage to the hypothalamus, from events like trauma or brain tumors, and cause accelerated weight gain, hyperphagia and lowered energy expenditure.
Imcivree, an MC4 receptor agonist, is already FDA-approved for several obesity-related rare diseases. The first came in 2020 for patients with POMC, PCSK1 or LEPR deficiency, rare genetic conditions that impair the MC4 pathway. In 2024 patients as young as two years old with those specific genetic conditions also gained access to Imcivree. In 2022 the drug got a label expansion to cover Bardet-Biedl syndrome, a rare genetic condition that causes hyperphagia and severe obesity.
“Looking ahead,” Stifel analysts wrote, “these [new] data should derisk HO [hypothalamic obesity] approval, and we see HO as a blockbuster opportunity with the potential for a fast ramp, per KOLs.”
