ODP606 Long-term Efficacy of Setmelanotide in Patients With Bardet-Biedl Syndrome

Abstract Objective Bardet-Biedl syndrome (BBS) is a rare genetic disease characterized by hyperphagia (pathologic insatiable hunger) and early-onset, severe obesity believed to be driven by impaired signaling in the melanocortin-4 receptor (MC4R) pathway. In a Phase 2 and a pivotal Phase 3 trial, treatment with the MC4R agonist setmelanotide produced beneficial reductions in weight, body mass index (BMI), BMI Z score, and hunger in patients with BBS at ∼1 year. The current analysis is the first to assess the continued long-term efficacy of setmelanotide administration in patients with BBS over ∼2 years. Methods Patients with BBS aged ≥6 years were eligible for this observational long-term extension (LTE) trial (NCT03651765) if they completed an index trial in which they received setmelanotide and demonstrated clinical benefit and acceptable safety as determined by the investigator. Patients received up to ∼12 months of setmelanotide as part of the index trial and began the LTE immediately following completion of the index trial. Study visits occurred approximately every 3 months in the LTE trial. Study objectives included evaluating changes in body weight and assessing safety and tolerability. The current analysis reports outcomes after ∼1 year of additional setmelanotide administration during the LTE trial, relative to index trial baseline. Results As of October 29, 2021, 54 patients with BBS enrolled the index trial, including 28 patients <18 years old and 26 patients ≥18 years old. Among patients who entered the LTE trial, 30 and 19 received at least 18 and 24 months of treatment, respectively. At their enrollment in their index trial, participants’ baseline mean (standard deviation [SD]) BMI was 42.2 (9.2) kg/m2, body weight in patients ≥18 years old was 132.3 (20.9) kg, and BMI Z score in patients <18 years old was 3.5 (0.76). Across age groups, after 18 and 24 months of treatment, mean (SD) percent change in BMI was −9.5% (10.5%; n=30) and −14.3% (11.6%; n=19), respectively. Mean (SD) percent change in body weight in those ≥18 years old after 18 and 24 months was −8.6% (10.3%; n=15) and −14.9% (10.4%; n=6), respectively. The mean (SD) change in BMI Z score in patients <18 years old after 18 and 24 months was −0.83 (0.50; n=13) and −0.72 (0.54; n=12), respectively. No new safety signals were observed during long-term setmelanotide administration. One patient discontinued because of an adverse event (hallucination; unlikely to be related to setmelanotide). Conclusions Clinically beneficial effects of setmelanotide on body weight-related measures continued to be observed in patients with BBS for up to 2 years. Only 1 patient discontinued the LTE trial due to an adverse event, suggesting setmelanotide continued to have clinical benefit and was generally well tolerated. These data support the long-term use of setmelanotide in patients with BBS. Presentation: No date and time listed