Rhythm doesn’t miss a beat as obesity drug clears phase 3 test

Rhythm Pharma says it has reported positive results for its obesity drug setmelanotide in two phase 3 trials, setting up regulatory filings later this year or in early 2020.

The two trials – in patients with pro-opiomelanocortin (POMC) deficiency and leptin receptor (LEPR) deficiency obesities – both showed that the melanocortin-4 receptor agonist had a “statistically significant and clinically meaningful effect on weight loss” compared to placebo.

Eight out of 10 patients in the POMC group experienced 10% or greater weight loss over a year, as did five out of 11 patients with LEPR obesity. It would be expected that patients would have gained weight over that period, but as it turned out the average weight loss in the two patient groups was 32 kg and 17 kg, respectively.

Rhythm said on a conference call that there was some suggestion that three LEPR patients who did not meet the 10% weight reduction threshold failed to receive a full dose of the drug.

The drug was also able to significantly reduce ‘insatiable’ hunger – leading to excessive eating or hyperphagia – in the trial. Obesity caused by these deficiencies tends to start in the first few months of life and be very severe, and is characterised by constant hunger pangs.

Both POMC and LEPR obesity are rare conditions, but are highly resistant to current therapies. Shares in Rhythm spiked after the results were announced, and analyst Michael Higgins of Ladenburg Thalmann now thinks the drug looks approvable with “convincing data” and an expected six-month review from the FDA.

He is predicting sales of just under $500m in 2026, with possible follow-up indications in other genetic obesity forms including Bardet-Biedl syndrome (BBS) and Alström syndrome, which could drive the total in that year above $1.2bn.

Higgins added however that achieving those sales will depend on robust systems to identify patients with genetic obesities, who are estimated to number only around 8,000 individuals in the US. Rhythm is developing screening tools to try to find eligible subjects.

Another 20,000 or so have heterozygous obesity – in other words carrying just one mutation rather than two – and Rhythm is currently running a phase 2 trial in this group.

“We believe this milestone moves us closer to delivering a treatment for numerous MC4R pathway-driven disorders of obesity,” said Rhythm’s chief executive Keith Gottesdiener.

“We are working to advance setmelanotide to its first regulatory submission in POMC and LEPR deficiency obesities,” he went on, noting that a filing with the EMA in Europe will follow after the FDA dossier.