Rhythm Pharma Reports Success in Two Late-Stage Trials for Genetic Obesity Disorders


Boston-based Rhythm announced positive topline data from two Phase III clinical trials of setmelanotide, its melanocortin-4 receptor (MC4R) agonist. The trials evaluated the drug for the treatment of pro-opiomelanocortin (POMC) and leptin receptor (LEPR) deficiency obesities.

Both trials met their primary endpoints as well as all key secondary endpoints. They showed statistically significant and clinically meaningful effect on weight loss and decreases in insatiable hunger, called hyperphagia, in both types of obesity.

“We believe these statistically significant data demonstrate setmelanotide’s ability to induce marked weight loss and substantially reduce hunger and we are excited about the potential difference we can make in the lives of people with rare genetic disorders of obesity,” stated Keith Gottesdiener, Rhythm’s chief executive officer. “We believe these pivotal data are the first step towards making a positive impact for people affected by rare genetic disorders of obesity who have grown up with insatiable hunger and early-onset, rapid weight gain that often leads to debilitating comorbidities. We believe this milestone moves us closer to delivering a treatment for numerous MC4R pathway-driven disorders of obesity. We are working to advance setmelanotide to its first regulatory submission in POMC and LEPR deficiency obesities.”

Click to sign up for job alerts

The company hopes to complete its rolling submission of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for both POMC and LEPR deficiency obesities before the end of the year or in the first quarter of 2020. It plans to request priority review, which would give it a six-month review process. It also expects to apply with the European Medicines Agency (EMA).

These types of obesities are marked by severe, early-onset obesity and insatiable hunger. The MC4R pathway is a significant component of the biological process that regulates hunger and body weight. Gene variations within the MC4R pathway are linked to several rare generic obesity disorders.

Gene variations in the POMC or PCSK1 genes can lead to severe obesity, insatiable hunger, endocrine abnormalities, red hair and light skin pigmentation.

Variations in the LEPR gene can lead to severe obesity, insatiable hunger, and endocrine abnormalities like hypogonadotropic hypogonadism and hypothyroidism.

Genetic diseases of obesity are Rhythm’s focus. Setmelanotide is being investigated for several other types of genetic obesities, including Bardet-Biedl Syndrome, Alstom Syndrome, POMC heterozygous deficiency obesity and POMC epigenetic disorders. It also is developing RM-853 for Prader-Willi syndrome, caused by a deletion on chromosome 15 that, among many things, leads to insatiable hunger and obesity.

On its second-quarter financial report on July 29, Rhythm indicated it had cash, cash equivalents and short-term investments of $195.2 million and research-and-development expenses were $35.3 million for the second quarter, compared to $8.6 million for the second quarter of 2018. It reported a net loss of $42.8 million for the second quarter and SG&A expenses were $8.8 million for the quarter.

Also in July, the company launched Uncovering Rare Obesity, a genetic testing program to broaden access to genetic testing and to discover the underlying genetic cause of severe obesity. It will also identify patients who may be eligible to participate in the company’s clinical trial programs.

Back to news