Rhythm Pharmaceuticals’ push to move obesity patients from jabs to tabs has stayed on beat. A phase 2 trial of the biotech’s next-generation oral candidate hit its primary endpoint, sending the stock up 26%.
Investigators randomized 28 people with acquired hypothalamic obesity—weight gain triggered by injury to the hypothalamus—to receive one of three doses of the MC4R agonist bivamelagon or placebo. After 14 weeks of oral dosing, Rhythm saw dose-dependent BMI reductions of up to 9.3% in people taking the study drug, compared to a 2.2% increase in the placebo arm.
Rhythm compared the results to data from setmelanotide trials. Phase 2 and 3 trials of setmelanotide, a daily injectable treatment that Rhythm markets as Imcivree, reported BMI reductions of 9.7% and 10.5%, respectively, after 12 and 16 weeks of treatment.
One patient stopped taking bivamelagon after having rectal bleeding. Three patients taking the study drug, plus one person on placebo, reported mild, localized hyperpigmentation. Rhythm cited the lack of hyperpigmentation—a condition that makes some areas of the skin darker than others—as a strength of bivamelagon when it licensed the drug candidate from LG Chem last year.
Rhythm identified participants who may not have fully complied with the treatment regimen, potentially because of difficulties swallowing three large pills a day. The biotech is developing a new, smaller tablet to try to address the problems.
Development is advancing in parallel with talks with the FDA that could lead to the start of a phase 3 trial next year. Rhythm CEO David Meeker, M.D., discussed expectations for the phase 3 trial on a call with analysts on Wednesday. Meeker is hoping the FDA agrees to a six-month double-blind period, reflecting knowledge of the mechanism and severity of the disease, but expects to need one year of safety data.
If the phase 3 trial succeeds, bivamelagon could form part of a two-pronged lineup of next-generation products at Rhythm. The other prong is RM-718, a weekly subcutaneous MC4R agonist. If both products come to market, Meeker said Rhythm won’t push people to one medicine or the other. The CEO expects patient preferences to shape whether people opt for the oral or injectable.
Meeker expressed confidence that patients will switch from Imcivree to either the daily oral or weekly subcutaneous product, even when generic competitors of the existing daily injectable come to market.
“The switch will happen because patients see [these] as preferred treatments. I don't think we'll need to convince people to do that,” Meeker said. “The incumbent first mover has an enormous advantage here. If and when a competitor comes in, they’ll tend to price similarly and then just go out and compete for share. And in that setting, we'll do fine.”
Rhythm’s stock opened up 26% at $82.18 in early trading Wednesday morning.