Rhythm Pharmaceuticals, a global biopharmaceutical company targeting rare neuroendocrine diseases, has announced that its Phase 3 EMANATE trial of setmelanotide did not meet the primary endpoints across its four substudies.

 

“We are grateful to the patients with rare, genetically-driven MC4R pathway diseases and investigators who participated in this trial,” said David Meeker, Chair, President and Chief Executive Officer of Rhythm Pharmaceuticals. 

 

“While we are disappointed the EMANATE substudies did not meet their primary endpoint, we are encouraged by compelling signals from additional analyses of the heterozygous POMC/PCSK1 and SRC1 substudies and learnings that sharpen our ability to identify true loss-of-function variants and inform the development of our next-generation MC4R agonists in rare genetically driven obesity indications.”

 

Meeker emphasized the ongoing need for treatments in this patient population. “These patients continue to face a profound unmet medical need, with no approved treatment options that target the underlying biology of their disease. These results provide important insights that support our commitment to advancing targeted therapies for patients with rare genetic obesities.”

 

The EMANATE trial was a global, randomized, double-blind, placebo-controlled Phase 3 study designed to assess the efficacy and safety of setmelanotide in patients with rare, genetically-driven MC4R pathway obesities. 

 

The study included four independent genetic substudies targeting obesity caused by heterozygous variants in the POMC/PCSK1, LEPR, SRC1 (NCOA1), and SH2B1 genes, with participants randomized 1:1 to receive setmelanotide or placebo for 52 weeks.