Rhythm Presents New Data for Setmelanotide in Multiple Rare Genetic Diseases of Obesity

Rhythm Pharmaceuticals presented a subgroup analysis of phase 3 data of setmelanotide (marketed as Imcivree) that showed a statistically significant weight loss and hunger reduction compared to placebo in patients with Bardet-Biedl syndrome (BBS) during a 14-week, double-blind treatment period.

Photo: Linda Shapiro, chief medical officer of Rhythm

The findings were among a series of presentations the company and its collaborators made of data and analysis from phase 2 and 3 data of Imciviree in a variety of genetic obesities during the 59^th Annual European Society for Paediatric Endocrinology meeting.

Setmelanotide targets the MC4 receptor pathway, a neural pathway responsible for regulating hunger, energy expenditure, and body weight. The genetic variants in people with these conditions impairs the MC4 receptor pathway and as a result they feel extreme, insatiable hunger and that causes early-onset, severe obesity.

In November 2020, Rhythm won approval for setmelanotide for people age 6 and older with obesiity due to due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.

In December 2020, Rhythm announced that its phase 3 trial evaluating setmelanotide in patients with BBS and Alström syndrome met its primary endpoint and all key secondary endpoints, with statistically significant and clinically meaningful reductions in weight and hunger at 52 weeks on therapy. All primary endpoint responders were patients with BBS; no patients with Alström syndrome met the primary endpoint.

Rhythm recently submitted a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) and remains on track to submit a type II amendment to the European Medicines Agency (EMA) in the fourth quarter of 2021 for both BBS and Alström syndrome.

The presentations also included complete topline analyses from the exploratory phase 2 basket trial that showed setmelanotide achieved clinically meaningful weight loss or BMI-Z reduction in 30 percent (9 of 30) of study participants with obesity due to variants of the SRC1 gene.

It also included complete topline analyses from the exploratory phase 2 basket trial that showed setmelanotide achieved clinically meaningful weight loss or BMI-Z reduction in 43 percent (15 of 35) of study participants with obesity due to variants of the SH2B1 gene, including 16p11.2 chromosomal deletions.

“Collectively, these presentations depict setmelanotide’s potential to deliver meaningful benefit – even without change in exercise or diet—to people with obesity and variants in the SRC1 or SH2B1 gene, both of which are included in our phase 3 EMANATE trial,” said Linda Shapiro, chief medical officer of Rhythm. “They support our decision to enroll people with obesity and variants in at least one of 31 other genes, all of which have ‘strong’ or ‘very strong’ MC4R pathway relevance, in our phase 2 DAYBREAK trial.”

Shapiro said the company will initiate both EMANATE and DAYBREAK in the fourth quarter, which will evaluate setmelanotide on top of standard of care dietary and physical activity guidance, as the company works to broaden setmelanotide’s reach to more patients with rare genetic diseases of obesity caused by variants in the MC4R pathway.

Author: Rare Daily Staff