Clinical Data Updated Interim Clinical Data from Phase 2 Basket StudyRhythm today announced new proof-of-concept interim data from its ongoing Phase 2 Basket Study across individuals with one of three distinct rare genetic diseases of obesity: HET obesity due to a genetic variant in one of the two alleles of the POMC, PCSK1 or LEPR gene (HETs); obesity due to SRC1 deficiency (SRC1); and obesity due to SH2B1 deficiency (SH2B1). Across five cohorts, 65 patients with severe obesity were eligible for analysis as of a cutoff date of Dec. 17, 2020.The primary endpoint of the study is the percent of patients in each subgroup showing at least a 5 percent loss of body weight over three months.HET Obesity (POMC, LEPR, PCSK1) highlights include:

• Overall, 12 of 35 patients (34.3 percent) achieved the primary endpoint. This full analysis includes six patients who withdrew early.
• Mean reduction from baseline in body weight across all 35 patients was -3.7 percent, which includes both clinical responders and non-responders;
• Among the 12 patients who achieved the primary endpoint (responder group), the mean reduction from baseline in body weight was -10.1 percent;
• Patients with HET obesity were stratified into three pre-specified cohorts by classification of their genetic variants according to American College of Medical Genetics (ACMG) guidelines:
  • Four of eight patients (50.0 percent) with a pathogenic or likely pathogenic variant achieved greater than 5 percent weight loss;
  • Four of eight patients (50.0 percent) with the N221D variant of the PCSK1 gene achieved greater than 5 percent weight loss;
  • Four of 19 patients (21.1 percent) with a variant of unknown significance (VOUS) achieved greater than 5 percent weight loss.
    

Data from the SRC1 and SH2B1 cohorts were based on an interim analysis of patients who completed 12 weeks of therapy. This analysis did not include 15 patients who withdrew early due to COVID-related issues, adverse events or were lost to follow-up. Also not included were data from 12 patients who remain ongoing but have not yet reached 12 weeks of therapy.Obesity due to SRC1 deficiency highlights include:

• Four of 13 patients (30.8 percent) achieved the primary endpoint;
• Mean reduction from baseline in body weight across all 13 patients was -3.7 percent, which included both clinical responders and non-responders;
• Among the four patients who achieved the primary endpoint (responder group) the mean reduction from baseline in body weight was -8.4 percent.
  

Obesity due to SH2B1 deficiency highlights include:

• Nine of 17 patients (52.9 percent) achieved greater than 5 percent weight loss over 12 weeks of therapy;
• Mean reduction from baseline in body weight across all 17 patients was -3.9 percent, which included clinical responders and non-responders;
• Among the nine patients who achieved the primary endpoint (responder group), the mean reduction from baseline in body weight was -7.1 percent.