Rhythm Pharmaceuticals, Inc. announced plans to add a cohort of patients with hypothalamic obesity in Japan to its ongoing global Phase 3 clinical trial of setmelanotide, with dosing expected to begin in the third quarter of 2024. Rhythm estimates that there are approximately 5,000 to 8,000 patients in Japan with hypothalamic obesity, a rare form of obesity that occurs following damage to the hypothalamic region of the brain, which includes the melanocortin-4 receptor (MC4R) pathway and is responsible for controlling physiological functions such as hunger and weight regulation. The condition most frequently follows the growth and surgical removal or other treatment of craniopharyngioma, astrocytoma, or other rare brain tumors.

These individuals often experience rapid weight gain, a reduction in energy expenditure, and an increase in hunger leading to severe obesity within six to 12 months following the hypothalamic lesions. The Company and Japan?s PMDA agreed to add a cohort of 12 Japanese patients to the ongoing trial and, pending completion of the trial, to use these data as part of the Company?s registration package to seek approval from Japan?s Ministry of Health, Labor and Welfare. In addition to efficacy data, Rhythm will collect and submit pharmacokinetics (PK) data from Japanese patients, expediting the typical pathway of collecting such data from an earlier-stage trial in Japanese subjects.

Rhythm also announced that it completed enrollment in the pivotal, 120-patient cohort in its global Phase 3 trial of setmelanotide in hypothalamic obesity with patients, aged 4 years or older with hypothalamic obesity randomized 2:1 to setmelanotide therapy or placebo for a total of 60 weeks, including up to eight weeks for doseration. As agreed to with both the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), Rhythm's regulatory submissions would be based on data from this cohort. The additional 12-patient Japanese cohort will not affect timing for regulatory submissions in the United States or Europe.

The Company remains on track to obtain top-line study results in the first half of 2025.