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Acquired hypothalamic obesity results from certain types of brain damage and holds a U.S. patient population of about 10,000, Rhythm Pharmaceuticals estimates. Rhythm Pharmaceuticals is switching up the tempo for its melanocortin-4 receptor (MC4R) agonist Imcivree. After its initial approval more than five years ago to treat certain patients with genetic-driven obesity, the drug is moving into a different and broader realm with an FDA nod for acquired hypothalamic obesity (HO). Acquired HO, for which Imcivree is the first approved treatment, represents an “expanded thinking” on the weight-regulating MC4R pathway that Rhythm’s product targets, Chief Scientific Officer Alastair Garfield, Ph.D., explained in a recent interview with Fierce. Until now, all of Imcivree’s approved uses have centered around specific genetic causes. HO, on the other hand, is a result of a hypothalamic injury such as a tumor or stroke that impairs the MC4R pathway and causes weight gain and insatiable hunger (hyperphagia).Imcivree scored its first FDA approval in 2020 to treat obesity due to genetically confirmed POMC, PCSK1 or LEPR deficiencies. Then, two years later, it added monogenic obesity due to Bardet-Biedl syndrome to its label.Moving outside of its bread-and-butter of genetic diseases is “a bit of a watershed moment” for Rhythm, Garfield said, presenting a “step-change in market potential” for the drug. The company estimates there’s an acquired HO patient population of about 10,000 in the U.S, a figure picked up from literature, tumor registries and claims data, Rhythm said in a press release. As part of its launch in the indication, Rhythm is placing importance on educating physicians and patients who might have the condition. Garfield anticipates the drug’s reach in the indication will be “a bit of a growth story,” but, as for a global patient spread, he thinks the company can “find these patients wherever we go looking.” Imcivree’s FDA approval was supported by Rhythm’s phase 3 Transcend trial, which saw a mean 18.4% improvement in body mass index (BMI) changes for Imcivree-treated patients. The mean BMI change from baseline came out to a 15.8% reduction for those taking the treatment, compared with a 2.6% BMI increase in the placebo group, according to the company. “This is a transformative milestone for Rhythm and reinforces our commitment to bringing meaningful therapies to patients living with rare MC4R pathway diseases,” CEO David Meeker, M.D., said in the company’s release.  The new label specifically allows Imcivree’s use to reduce excess body weight and maintain reductions over the long term in adults and pediatric patients aged 4 years and older with acquired HO. In a note to clients, Leerink analysts called the nod a “significant label expansion” that bolsters the company’s leadership position in the genetic obesity space. The approval brings Rhythm to a “major inflection point,” the analysts wrote, noting that the company has “successfully transitioned from an R&D-stage biotech to a commercial-stage company with durable revenue visibility.”Imcivree is Rhythm’s sole commercial product and garnered $194.8 million in 2025 sales.The FDA’s blessing in acquired HO marks a welcome reprieve from a trial fail Rhythm reported earlier this week, which ended its hopes of expanding into a different subset of genetic obesities. Still, considering how “pivotal” the MC4R pathway is to defining body weight, “I think there are many more places where we’re going to learn in time our approach is going to be the most effective,” Garfield said. The executive spoke with Fierce Pharma before the latest results dropped.  As it stands, a potential expansion into Prader-Willi syndrome is “front and center for us,” Garfield noted.   Obesity lessons Rhythm cracked into the obesity space in its small genetic corner before Eli Lilly and Novo Nordisk busted the market wide open with their popular GLP-1 products for general obesity. When Lilly and Novo’s drugs rose to widespread popularity a few years back, Rhythm ultimately learned a “very valuable lesson,” Garfield said.“We were concerned we were going to be the proverbial damsel in distress,” Garfield said, painting a picture of the smaller pharma “tied to the railway tracks as these two juggernauts of Novo and Lilly came careening across us.” Instead, Rhythm came to find out that “a rising tide lifts all boats,” Garfield said, referring to how the GLP-1s have increased awareness and interest in obesity therapeutics. Of course, that increased awareness comes with further education to be done on the differences between hyperphagia and general obesity and battling the notion that all obesity is the same. But, with additional awareness and proof that the MC4R mechanism works in the “right” populations, Rhythm can “put a moat around our patient populations,” Garfield said. In the future, he expects obesity to become an "umbrella term" with well-defined subsets underneath the broader definition. 

Plus, news about Gilead, Assembly Biosciences and Pfizer: 📁 Sarepta says FDA open to a filing for full approval of two Duchenne drugs: After a failed confirmatory study for its two exon-skipping drugs Amondys 45 and Vyondys 53, Sarepta is moving ahead with an application to the FDA by the end of April to ask for both drugs to be converted from accelerated to traditional approvals. Sarepta said it met with the FDA and the agency confirmed the company could submit its data from the failed study, ESSENCE, as well as real-world evidence. — Lei Lei Wu 🟢 Rhythm Pharmaceuticals gets approval in rare form of obesity: The MC4R agonist Imcivree has become the first FDA-approved therapy for acquired hypothalamic obesity, a condition in which patients rapidly gain weight following an injury to the brain. Cowen analysts wrote on Friday that they expect Imcivree to be adopted as standard of care. They added that doctors they had surveyed expect 24% of patients with hypothalamic obesity to be on Rhythm’s drug within its first year on sale. The analysts project sales of $42 million in 2026, rising to $860 million in 2030. Imcivree was already approved for a handful of rare genetic disorders that cause obesity, but on Monday, it failed in a study of other genetically driven forms of the disease. — Elizabeth Cairns ↩️ Gilead turns down hep B drug: Gilead has decided not to take forward a candidate for hepatitis B virus under a long-running partnership with Assembly. Gilead held an option on the candidate as part of a deal announced in 2023. But on Thursday, Assembly said Gilead “declined to exercise or defer its option.” Assembly did, however, get a $35 million option fee from licensing its helicase-primase inhibitor program to Gilead. — Nicole DeFeudis ✂️ Pfizer culls antibody-drug conjugate in Phase 1 testing: The company discontinued the program, called PF-08046031, due to a “business decision,” a Pfizer spokesperson said. The program targets CD228 and was acquired through Pfizer’s 2023 buyout of Seagen. Researchers were testing PF-08046031 in advanced melanoma and other solid tumors. — Max Gelman