Skye Bioscience’s obesity candidate has failed to reduce weight in a phase 2 study, marking another setback for the CB1 inhibitor class.
The biotech had been evaluating a 200-mg weekly subcutaneous dose of the drug, called nimacimab, as a monotherapy and in combination with semaglutide—the ingredient in Novo Nordisk’s blockbuster Wegovy—compared to semaglutide alone in the midstage trial of 136 patients who are overweight or with obesity.
Nimacimab alone demonstrated weight loss of just 1.52%, barely above the placebo group’s 0.26% weight reduction and a fraction of the 10.25% weight loss seen among the semaglutide cohort. Shares in the company tumbled Monday morning, down more than 60% in early premarket trading.
Skye Chief Medical Officer Puneet Arora, M.D., suggested “lower-than-expected drug exposure” from the 200-mg dose “may have limited the observed effect.”
Instead, the biotech was keen to point to the 13.2% average weight loss among patients taking the nimacimab-semaglutide combo.
“The combination of nimacimab with semaglutide produced a clinically meaningful additional weight loss that exceeded semaglutide alone, with a favorable tolerability profile even in patients who achieved the highest exposure levels,” Arora said in the Oct. 6 release.
“With our preclinical data, toxicology safety margins, and PK modeling, we believe we have a path to support higher dosing, and we are evaluating the next stage of development to optimize dosing in potential future clinical trials," the CMO added.
It marks the latest setback for hopes of getting a CB1 blocker to market as a weight loss treatment. Sanofi had a CB1 obesity drug approved in Europe, but authorities withdrew the approval in 2009 after studies found it doubled the risk of psychiatric disorders. More recently, Roche took a chance on the modality when the Swiss pharma penned a $1.1 billion deal for Inversago Pharma in 2023.
The lead drug from that study was also tied to neuropsychiatric side effects. Roche went on to drop a second CB1 drug from Inversago, although there were no signs of similar side effects influencing that decision.
In this morning’s release, Skye stressed that “no neuropsychiatric concerns were observed” in its phase 2 study of nimacimab. In fact, the drug demonstrated a “clean” safety profile, according to the biotech, with none of the increased gastrointestinal adverse events seen with some weight loss drugs.
More than a quarter of patients across the trial discontinued their treatment, including 30% of the placebo cohort, 29% of the nimacimab monotherapy group and 26% of those who received the nimacimab-semaglutide combo. However, only 3.7% of discontinuations were due to adverse events, Skye said.
Undeterred by this morning’s top-line fail, Skye pointed to “multiple factors” it believes justify evaluating the drug at higher doses and alluded to a potential fresh phase 2a study down the line.