Rhythm Completes Enrollment Screening for Setmelanotide Phase 3 Obesity Trial with Updates

Rhythm Pharmaceuticals Inc. (Nasdaq: RYTM), a global biopharmaceutical firm focused on rare neuroendocrine diseases, recently announced the completion of the enrollment screening for its pivotal Phase 3 trial of setmelanotide in patients with acquired hypothalamic obesity. This Phase 3 clinical trial aims to assess setmelanotide's efficacy among more than 140 patients, aged 4 and older, who will be randomized in a 2:1 ratio to receive either setmelanotide or a placebo over 60 weeks, including up to eight weeks for dose titration. The company anticipates releasing top-line results by the first half of 2025.

David Meeker, M.D., Chair, President, and CEO of Rhythm, highlighted 2023 as a landmark year with significant advancements in their commercial and developmental objectives for setmelanotide. The rapid enrollment for the Phase 3 trial underscores the pressing need for an effective treatment and the community’s optimism about setmelanotide's potential.

Furthermore, Rhythm announced a positive development regarding reimbursement approvals for IMCIVREE® (setmelanotide) in Spain. This approval pertains to treating obesity and controlling hunger associated with Bardet-Biedl syndrome (BBS) and specific genetic deficiencies such as POMC, PCSK1, and LEPR.

Yann Mazabraud, Executive Vice President and Head of International at Rhythm, expressed satisfaction with Spain's Ministry of Health’s decision, noting it as a crucial step in providing care to patients with hyperphagia and early-onset obesity connected to BBS and POMC/LEPR deficiencies. These rare disorders are typified by excessive hunger and severe obesity from an early age. Additional symptoms for BBS include cognitive impairment, renal dysfunction, and visual issues. While POMC and LEPR deficiencies are exceedingly rare, BBS remains somewhat under-diagnosed yet more identifiable.

In another development, the FDA has accepted Rhythm's Investigational New Drug (IND) application for RM-718. This new, weekly treatment aims to be a more targeted and potent variant than setmelanotide, with a potential reduction in side effects such as hyperpigmentation. The company plans to initiate Phase 1 trials, including a multiple-ascending dose study in hypothalamic obesity patients, in the first half of 2024.

Rhythm Pharmaceuticals, headquartered in Boston, MA, is committed to transforming the lives of those with rare neuroendocrine diseases. Their flagship product, IMCIVREE® (setmelanotide), approved by the FDA for chronic weight management in patients with certain genetic conditions, aims to treat severe obesity and hyperphagia. The European Commission and the UK’s Medicines & Healthcare Products Regulatory Agency also authorize its use for obesity and hunger control in genetically confirmed cases.

Setmelanotide has specific indications and limitations in its use, primarily prescribed under the supervision of physicians experienced in managing genetically-linked obesity. It is not recommended for conditions lacking a genetic basis in POMC, PCSK1, LEPR deficiencies, or BBS, nor for general obesity.

Patients using setmelanotide should undergo regular skin examinations, as the drug may increase skin pigmentation. Monitoring of heart rate and blood pressure is also advised, due to potential side effects such as prolonged penile erections and depression. For the pediatric population, growth monitoring is essential.

There are potential risks concerning setmelanotide use during pregnancy and breastfeeding. While animal studies have shown no direct reproductive harm, the drug should be used during pregnancy only if absolutely necessary. The presence of benzyl alcohol as an excipient might pose metabolic acidosis risks, particularly for those with hepatic or renal impairment.

Common adverse reactions include hyperpigmentation, injection site reactions, nausea, and headache. While data on setmelanotide's impact on human fertility are unavailable, animal studies suggest no harmful effects.

These trials and approvals signal a promising future for Rhythm Pharmaceuticals in addressing severe obesity and related conditions through targeted genetic therapies.