Phase 3 Setmelanotide Trial in Bardet-Biedl, Alström Syndromes Completes Enrollment
A Phase 3 clinical trial testing setmelanotide as a treatment for insatiable hunger and severe obesity in people with Bardet-Biedl syndrome (BBS) and Alström syndrome has completed enrollment for its pivotal group of participants.
As with other genetic obesity disorders, BBS and Alström syndrome are caused by variants in the genes that are part of the melanocortin-4 receptor (MC4R) pathway. This pathway helps regulate hunger and satiety, or feeling full. Setmelanotide binds to MC4R, and is intended to activate this pathway to help regulate satiety and hunger.
The Rhythm-sponsored Phase 3 study (NCT03746522) will test setmalonotide in 32 people with BBS and 6 with Alström syndrome. Participants will be randomly assigned to receive daily treatment with either 3 mg setmelanotide or a placebo, both given via under-the-skin injection over 14 weeks. Then, all patients will receive setmelanotide for 38 more weeks, completing one year (52 weeks) of treatment.
The trial’s primary goal is the proportion of participants, ages 12 and older at the start of the trial (baseline), who lose at least 10% of their body weight. The analysis will be done at the 52-week point.
An additional 14-week period of treatment with setmelanotide will follow, after which participants will have the option to enroll in a separate extension trial.
“With no approved treatment options available, there is a pressing need for a new therapy that addresses the insatiable hunger and severe obesity that people living with BBS or Alström syndrome may experience,” said Murray Stewart, MD, Rhythm’s chief medical officer.
“We look forward to continuing to partner with the BBS and Alström syndrome communities as we work to identify patients, better understand the long-term burden of these disorders and advance this pivotal trial toward topline data in the fourth quarter of 2020 or early in the first quarter of 2021,” he added.
Recent results of an ongoing Phase 2/3 trial (NCT03013543) have shown that setmelanotide leads to significant weight loss and less hunger at two years of treatment in patients with BBS and Alström syndrome.
That study also is addressing the experimental therapy’s potential benefits in people with other genetic obesity conditions. These include POMC deficiency, LEPR deficiency, SRC1 deficiency, SH2B1 deficiency, MC4R deficiency, and Smith-Magenis syndrome — all of which involve the MC4R pathway.
Two other Phase 3 trials are testing setmelanotide in people with POMC deficiency (NCT02896192) and LEPR deficiency (NCT03287960). Updated results have revealed that setmelanotide decreased body mass index at one year of treatment in participants with either of these disorders.