FDA Expands Approval of Rhythm’s Imcivree

Rare Daily Staff

The U.S. Food and Drug Administration has granted expanded approval to Rhythm Pharmaceuticals’ obesity drug Imcivree, making it the first and only therapy cleared to treat people with the rare condition acquired hypothalamic obesity.

The FDA’s decision allows the drug, known generically as setmelanotide, to be used to reduce excess body weight and help maintain weight loss in adults and children age 4 and older who have this form of obesity.

Acquired hypothalamic obesity is a rare, severe disorder that can develop after damage to the hypothalamus, a small region deep in the brain that helps control hunger, energy use, and body weight. The condition often follows treatment for brain tumors near the hypothalamus, such as craniopharyngioma or astrocytoma, but it can also result from traumatic brain injury, stroke, or inflammation. Patients typically experience rapid, persistent weight gain, intense and constant hunger, and low energy levels as the brain’s normal signals for appetite and metabolism are disrupted.

Imcivree is an MC4R agonist that activates this receptor to help restore signaling, increase feelings of fullness, and boost energy expenditure, which together can lead to reduced food intake and weight loss.

Imcivree is now approved in the United States to reduce excess body weight and maintain weight reduction in adults and children 4 and older with acquired hypothalamic obesity, and in adults and children 2 and older with certain rare genetic forms of obesity, including Bardet‑Biedl syndrome and specific deficiencies in POMC, PCSK1, or the leptin receptor.

In Europe and the United Kingdom, the drug is authorized for some of those genetic obesity conditions in patients as young as 2 and must be prescribed by physicians experienced in obesity with an underlying genetic cause.

The new approval is based on a global phase 3 study called TRANSCEND that enrolled 142 patients with acquired hypothalamic obesity. After 52 weeks of treatment, patients who received setmelanotide saw their body mass index (BMI) drop by an average of 15.8 percent, while those on placebo had a 2.6 percent increase, resulting in a placebo‑adjusted BMI reduction of 18.4 percent that was statistically significant.

Investigators reported that patients on the drug experienced meaningful reductions in both BMI and hunger, in children and adults.

Imcivree was generally well tolerated in the phase 3 trial. The most common side effects, occurring in more than 20 percent of participants, were skin darkening, nausea, vomiting, and headache. Imcivree carries warnings for potential disturbances in sexual arousal, depression and suicidal thoughts, serious allergic reactions, changes in skin pigmentation and moles, acute adrenal insufficiency in some patients with acquired hypothalamic obesity, and sodium imbalances in people who also have central diabetes insipidus.

“Imcivree is now the first and only FDA‑approved therapy for acquired HO, offering a targeted approach that addresses the underlying biology of this disease and meets a critical unmet need for patients who previously had no treatment options,” said David Meeker, president and CEO of Rhythm.

Photo: David Meeker, president and CEO of Rhythm