Rhythm Pharmaceuticals Begins Dosing in Phase 2 Trial of LB54640 for Hypothalamic Obesity

Rhythm Pharmaceuticals, Inc., based in Boston and listed on Nasdaq under the ticker RYTM, has announced the commencement of its Phase 2 clinical trial for LB54640, an investigational oral melanocortin-4 receptor (MC4R) agonist, aimed at treating hypothalamic obesity. LB54640 has previously demonstrated targeted efficacy on MC4R pathways without causing hyperpigmentation, an advancement closely watched by the medical community.

David Meeker, M.D., Chair, CEO, and President of Rhythm Pharmaceuticals, emphasized the importance of moving forward with LB54640, following promising preclinical results and a successful Phase 1 trial. Meeker expressed optimism about the potential of LB54640 as an effective oral therapy for MC4R pathway diseases, highlighting its capability to address hyperphagia and severe obesity. The goal is to provide patients with a comprehensive range of treatment options tailored to their specific needs.

The Phase 2 trial is designed as a randomized, placebo-controlled, double-blind study to evaluate the safety, efficacy, and impact on weight reduction, hunger, and quality of life in patients aged 12 and older diagnosed with hypothalamic obesity. A total of 28 patients will participate, receiving either low, middle, or high doses of LB54640 or a placebo over a 14-week period. The primary objective is to observe changes in body mass index (BMI) from baseline after 14 weeks, with an option to extend the treatment up to 52 weeks.

The development of LB54640 follows a global licensing agreement between Rhythm Pharmaceuticals and LG Chem, Ltd., established in January 2024. In earlier Phase 1 trials involving healthy overweight adults, LB54640 exhibited dose-dependent weight reduction and a favorable safety profile, with no significant changes in blood pressure or heart rate and no occurrences of hyperpigmentation.

Rhythm Pharmaceuticals focuses on transforming the lives of patients with rare neuroendocrine diseases. Their flagship product, IMCIVREE® (setmelanotide), is an MC4R agonist approved by the FDA for chronic weight management in adults and children six years and older with genetic obesity conditions such as pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiencies, as well as Bardet-Biedl syndrome (BBS). This approval is also recognized by the European Commission and the UK's Medicines & Healthcare Products Regulatory Agency (MHRA) for similar indications.

In addition to IMCIVREE®, Rhythm Pharmaceuticals continues to advance its clinical development pipeline, which includes investigational MC4R agonists like LB54640 and RM-718, along with a suite of preclinical small molecules aimed at treating congenital hyperinsulinism.

Setmelanotide's indication covers chronic weight management for specific genetic deficiencies and BBS in both the United States and Europe. The treatment is not suitable for obesity caused by benign or likely benign POMC, PCSK1, or LEPR variants, nor for other types of obesity, including polygenic obesity. It is contraindicated in patients with a history of serious hypersensitivity to setmelanotide or its excipients.

Safety warnings for setmelanotide include risks of skin pigmentation changes, heart rate and blood pressure monitoring, disturbances in sexual arousal, depression, and suicidal ideation. In Europe, pediatric patients' growth should be monitored, and the impact of weight loss on growth and maturation must be evaluated.

Common adverse reactions include skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, and spontaneous penile erection. Breastfeeding is not recommended during treatment with setmelanotide.

For adverse reaction reporting, patients and healthcare providers can contact Rhythm Pharmaceuticals or respective regulatory bodies in the United States and Europe.