The primary endpoint was the difference in mean percent change in BMI from baseline to Week 52 versus placebo, analyzed in the modified intent-to-treat (ITT) population. The topline results indicated a placebo-adjusted reduction in BMI of -4.3% for POMC/PCSK1 Hets (N=78, p=0.15), -3.6% for LEPR Hets (N=23, p=0.94), -4.0% for SRC1 (NCOA1) (N=73, p=0.12), and -1.7% for SH2B1 (N=121, p=0.43).
Despite the disappointing primary results, post hoc analyses revealed that setmelanotide achieved statistically significant and clinically meaningful BMI reductions at Week 52 in the modified ITT patient populations for the POMC/PCSK1 Hets and SRC1 substudies. Specifically, there was a -5.5% least-squares mean difference in BMI for POMC/PCSK1 Hets patients (n=78; p=0.0010) and a -6.2% difference for SRC1 (NCOA1) patients (n=73; p<0.0001).
Rhythm Pharmaceuticals noted that no new safety signals were observed in the EMANATE trial, and the safety profile was consistent with prior clinical studies. The most common treatment-emergent adverse events included skin hyperpigmentation, injection site reactions, nausea, vomiting, and headache. The company plans to continue analyzing the EMANATE dataset and evaluate potential clinical development paths forward with next-generation MC4R agonists bivamelagon and RM-718.
The results of the EMANATE trial are critical for Rhythm Pharmaceuticals as they navigate the complex landscape of rare genetic obesity treatments. The company remains committed to advancing targeted therapies for patients with rare genetic obesities, despite the challenges presented by the trial outcomes.
