Skye Bioscience's experimental obesity drug nimacimab failed to demonstrate significant weight loss as a standalone therapy in a mid-stage clinical trial, causing the San Diego biotechnology company's stock to plummet nearly two-thirds to under $2 per share. However, the CB1 cannabinoid receptor inhibitor showed promising results when combined with existing weight loss medications, potentially opening a new pathway for combination obesity treatments.
Monotherapy Results Fall Short of Expectations
In the 26-week Phase 2 trial, patients receiving nimacimab as monotherapy achieved only 1.5% weight loss compared to less than 0.3% for placebo recipients. The company attributed these disappointing results to dosing issues, stating that analysis revealed the 200 milligram weekly injection was "suboptimal as a monotherapy."
Skye Chief Medical Officer Puneet Arora noted that the drug's effects may have been limited by "lower-than-expected drug exposure," which could inform the company's future development strategy. The company plans to evaluate the data to determine next steps, including a potential "follow-on" Phase 2 study.
Combination Therapy Shows Enhanced Efficacy
Despite the monotherapy setback, nimacimab demonstrated superior performance when paired with semaglutide, the active ingredient in Novo Nordisk's Wegovy. In the combination arm of the study, patients lost just over 13% of their body weight compared to more than 10% for those receiving semaglutide alone.
Louis Aronne, a company advisor and past president of The Obesity Society, described the study results as the first evidence that drugs like nimacimab "can drive meaningful additional weight loss" beyond incretin therapies alone. The findings support the potential for future studies evaluating combinations of nimacimab with other incretin-based therapies widely used for weight loss.
Safety Profile Addresses Key Concerns
Nimacimab demonstrated "placebo-like tolerability" with no increase in gastrointestinal problems when combined with semaglutide. Importantly, there was no spike in psychiatric side effects with nimacimab, addressing a significant concern with CB1 inhibitor drugs of its class.
This safety profile could represent a significant advantage, as gastrointestinal side effects and muscle mass loss are notable weaknesses of current incretin therapies. According to analyst Andy Hsieh from William Blair, the CB1 inhibitor approach appears to spur weight loss with a lower degree of gastrointestinal side effects and retention of muscle mass.
CB1 Inhibition Strategy Faces Industry Challenges
Skye is among many companies attempting to improve upon popular weight loss drugs like Wegovy through additive therapies that might boost effects or address limitations. The company's approach involves blocking CB1, a cannabinoid receptor that regulates appetite.
However, this concept has yet to achieve clinical success across the industry. Last September, a CB1-inhibiting drug from Novo Nordisk failed to meet weight loss expectations, leading the company to conclude that "further work" was needed to optimize dosing.
According to Hsieh's research notes, Skye executives had been hoping the nimacimab-Wegovy combination would induce weight loss that was 5 to 8 percentage points better than Wegovy alone. While the observed 3 percentage point improvement falls short of these expectations, it represents the first clinical evidence of meaningful additive benefit from CB1 inhibition in combination with incretin therapy.
