Endocrine Abstracts

Background: Bardet-Biedl Syndrome (BBS) is a rare genetic disease in which impaired melanocortin-4 receptor (MC4R) signaling leads to hyperphagia and obesity. In an index Phase 3 trial, broad clinical benefit was observed in patients with BBS based on improvement or stabilization in ≥1 measure of weight, hunger, or quality of life with 1 year of treatment with the MC4R agonist setmelanotide. Reported here are long-term extension (LTE) weight outcomes after 3 years of setmelanotide.

Methods: Patients with BBS who achieved clinical benefit and tolerability in a prior trial of setmelanotide could enroll in the LTE (NCT03651765) and continue treatment for ≥5 years or transition to commercial product or other clinical trials. This analysis reports age-appropriate weight-related outcomes and adverse events for 3 years of setmelanotide treatment in patients who achieved clinically meaningful response at 1 year of index trial, defined as ≥10% weight reduction (age ≥18 years at baseline) or reduction of ≥5 percentage points in the percent of the BMI 95th percentile (%BMI₉₅; age <18 years at baseline).

Results: Of 32 patients who entered the LTE with clinically meaningful age-appropriate weight responses, 21 patients with 3-year measurements were included in the analysis. Eleven patients were excluded as 1 pediatric patient transitioned to adulthood before this analysis, 5 had <3 years of treatment, 2 transitioned to commercial therapy, and 3 discontinued treatment. Mean (SD) index trial baseline for body weight was 129.8 (21.3) kg in patients aged ≥18 years (n=10) and 148.7 (36.1) percentage points for %BMI₉₅ in patients aged <18 years (n=22); change at Year 3 was −22.0 (18.1) kg (n=8) and −19.4 (19.4) percentage points (n=13), respectively. No new safety signals were observed in the LTE.

Conclusions: Sustained meaningful benefit in weight-related measures at 3 years of treatment with no new safety signals supports continuous treatment with setmelanotide in patients with BBS.