With its first enrollee, Rhythm Pharmaceuticals has begun a pivotal Phase 3 trial to assess the therapeutic benefits of setmelanotide in patients with moderate-to-severe Bardet-Biedl syndrome (BBS) and Alström syndrome, two genetic obesity disorders.
Setmelanotide, formerly known as RM-493, is an investigational potent activator of the melanocortin-4 receptor (MC4R) under development to possibly treat rare genetic obesity disorders.
Through the activation of MC4R signals, researchers expect to regulate energy expenditure and excessive appetite (hyperphagia) in patients with obesity caused by rare genetic defects upstream of the MC4R, which lead to loss of this pathway’s function.
“We are encouraged by the continued progress across our development program for setmelanotide, including the enrollment of the first patient in our combined pivotal Phase 3 trial in BBS and Alström syndrome,” Murray Stewart, MD, chief medical officer of Rhythm Pharmaceuticals, said in a press release.
“This accomplishment reflects our commitment to the efficient development of setmelanotide as a potential first-in-class therapy for people living with MC4R pathway disorders,” Stewart added.
The Phase 3 trial (NCT03746522) plans to enroll up to 30 patients worldwide, ages 6 and up, and to include at least 20 with BBS and at least six with Alström syndrome. It is now enrolling, but currently only at a single site in Wisconsin, and expects to run through June 2020.
The study will have three treatment periods. In the first period, participants will be randomly assigned to receive daily injections of setmelanotide or a placebo for 14 weeks. In the second period, all patients will receive daily treatment with setmelanotide for an additional 38 weeks.
After completion of the 52 weeks, a primary data analysis will be made to evaluate the safety and efficacy of setmelanotide, as determined by a reduction of 10% or more in body weight compared to the start of the treatment.
If the analysis shows positive responses and no safety concerns, patients may elect to continue the treatment for 14 more weeks (the third period). At that point, they may enroll in a separate extension study, where all will continue to be treated.
“Many of our BBS patients struggle with insatiable hunger and severe obesity, which can be a challenging burden while also managing the disorder’s potential effects on vision, kidney function, and other organs,” said Robert M. Haws, MD, the trial’s principal investigator , and director of Clinical Research Center at the Marshfield Clinic Research Institute and of the Center of Excellence for Bardet-Biedl Syndrome. “We are eager to begin the pivotal Phase 3 trial as we continue to study setmelanotide’s potential to reduce body weight and hunger in these patients.”
Rhythm Pharmaceuticals is planning to recruit more patients, following enrollment of the last pivotal patient, to generate additional data regarding the safety and efficacy of the therapy in people with these diseases.
Setmelanotide was designated a breakthrough therapy by the U.S. Food and Drug Administration (FDA) for the treatment of obesity associated with genetic defects upstream of the MC4 receptor, including POMC deficiency obesity, LEPR deficiency obesity, BBS, and Alström syndrome. BBS is caused by changes, or variants, in several genes linked to the MC4R pathway; Alström is caused by variants in the ALMS1 gene. Both, by impacting the MC4R pathway, affect hunger signals in the brain.