The FDA has lifted the clinical hold on Biomea Fusion's Phase I/II and Phase II clinical trials, COVALENT-111 and COVALENT-112, respectively, evaluating BMF-219 in patients with type 2 diabetes (T2D) and type 1 diabetes (T1D). The decision follows a comprehensive safety review of the ongoing Phase IIb expansion study. The company's stock experienced a 9% increase at market close on September 26 following the announcement. The company expects to share topline data from the Phase IIa portion of COVALENT-112 and topline 26-week data from Phase IIb of COVALENT-111 in Q4 2024.
Background on the Clinical Hold
In June, the FDA paused the trials of BMF-219 following reports of potential drug-induced hepatotoxicity. This news led to a 65.57% decline in Biomea’s stock price. The clinical hold affected the Phase I/II COVALENT-111 trial (NCT05731544) and Phase II COVALENT-112 trial (NCT06152042) evaluating BMF-219 in patients with T2D and T1D, respectively.
Safety Review and Findings
According to Biomea’s CEO Thomas Butler, the FDA lifted the clinical hold based on a “safety review of the ongoing Phase IIb expansion study, where the concerning safety signals seen in the Phase IIa escalation study did not translate over to the larger expansion study.” He added that “none of the elevated lab values translated to confirmed serious liver injury or liver impairment.”
An independent review of the trial’s safety data indicated that liver enzyme elevations were predictable, dose-related, transient, and returned to baseline. High-grade elevations of liver enzymes occurred within the first 30 days in patients who received a starting dose of 200mg, particularly in those with high baseline blood glucose levels who experienced a rapid drop in blood sugar. Patients who received a 100mg dose or were escalated from 100mg after 60 days did not experience high-grade elevations of liver enzymes, regardless of baseline glucose levels.
Trial Design Modifications
The FDA has suggested trial design modifications, including a BMF-219 starting dose of 100mg once daily for all future diabetes studies, dose escalation only after initiation with 100mg, and increased monitoring of liver enzymes. The agency also advised the company to take a detailed patient history, including concomitant medications.
About BMF-219
BMF-219 is an investigational irreversible covalent inhibitor of menin. It inhibits menin's ability to interact with transcriptional partners that drive the expression of cell cycle protein regulators, including those that prevent the replication and expansion of beta cells. Apart from diabetes, BMF-219 is also being evaluated as a treatment for cancers, including leukaemia, in two Phase I trials (NCT05631574 and NCT05153330).
