Three months after Biomea Fusion’s menin inhibitor was released from a clinical hold, the company has claimed a win in a phase 2 diabetes trial.
The COVALENT-111 study enrolled 225 adults with Type 2 diabetes who had levels of HbA1c, a standard blood glucose measure, between 7% and 10.5%. These individuals received 100 mg of icovamenib either once daily for eight weeks, once daily for 12 weeks or once daily for eight weeks and then twice daily for another four weeks.
The program was interrupted when the FDA placed the study on hold in June in response to possible drug-induced liver damage in patients who received icovamenib in the dose-escalation portion of the phase 1/2 study. Biomea was given the go-ahead to continue in September under a revised protocol intended to mitigate liver toxicity concerns.
Biomea’s efficacy analysis relies on the 168 patients who had competed at least 80% of their dosing before the hold and had been treated with one or more anti-hyperglycemic therapies. Among this prespecified per-protocol patient population, the trial hit the primary endpoint of showing a “meaningful statistically significant placebo-corrected mean reduction in HbA1c,” Biomea said in the release.
Overall, these patients showed a mean reduction in HbA1c of 0.36%. Those patients who received daily dosing for 12 weeks performed best, with a mean HbA1c reduction of 0.5% at Week 26.
Biomea also drilled down into subgroups of patients with mild age-related diabetes and severe insulin-deficient diabetes, where the mean HbA1c reduction was 0.73%. These two subgroups account for more than half of the U.S. Type 2 diabetes population, the biotech pointed out.
“Of note, in the patients that failed on a GLP-1-based therapy, an HbA1c reduction of 0.84% was demonstrated,” the company added.
No serious adverse events or discontinuations due to adverse events were observed, Biomea said in the release.
Investors appeared underwhelmed by the results, sending the company’s shares down 14% to $5.04 in early trading Tuesday.
Biomea said it will wait for a 52-week readout in the second half of 2025 before taking its data to the FDA to discuss how to advance icovamenib toward approval.
"The topline data from the COVALENT-111 phase 2 study are incredibly promising, showing that icovamenib delivers significant and clinically meaningful reductions in HbA1c,” Chief Medical Officer Juan Pablo Frias, M.D., said in the release.
“This study confirms the potential of menin inhibition as a novel mechanism for treating type 2 diabetes,” Frias added. “Achieving a HbA1c reduction of this magnitude without chronic treatment is paradigm shifting in diabetes therapy.”