Biomea Fusion has escaped from the full clinical hold imposed by the FDA. After reviewing the data, the regulator has cleared Biomea to study its diabetes drug candidate under a revised protocol intended to mitigate liver toxicity concerns.
The FDA imposed a full clinical hold in June in response to possible drug-induced liver damage in Type 2 diabetes patients who received BMF-219 in the dose-escalation portion of Biomea’s phase 1/2 study. On a call with analysts Thursday, Biomea CEO Thomas Butler discussed what the company and the regulator learned after stopping the trial, and a second study, to review the data.
“The liver enzyme elevations are predictable, dose related, transient and return to baseline. High-grade elevations occurred in the first 30 days and were seen in patients with a starting dose of 200mg,” Butler said. “These patients typically had high baseline blood glucose levels and experienced a rapid drop in their blood sugar in the first 30 days.”
None of the elevated lab values translated to confirmed serious liver injury or liver impairment. No grade 3 or higher elevations were seen in patients who started on 100 mg, even if they escalated to 200 mg later in the trial.
In the expansion phase of a Type 2 diabetes study, Biomea gave more than 200 people the lower starting dose. No patients had grade 3 or higher liver enzyme elevations. Biomea saw “a very low incidence of grade 2 elevations,” Biomea Chief Medical Officer Juan Pablo Frías, M.D., said, and no dose interruptions or dose discontinuations.
The analysis has informed the next steps. On the FDA’s recommendation, Biomea has implemented a single-step escalation from 100 mg to 200 mg and increased monitoring to support patient safety. Future trials will have an increased focus on liver safety surveillance and the potential influence of concomitant medications and the patient’s medical history on safety.
“Patients that are taking, particularly new, drugs that are potentially hepatotoxic such as recently started antibiotics … [will] either be excluded or will wait until the course of that therapy is completed and the patient is stable,” Frías said.
Biomea is on track to review data from the Type 2 expansion trial toward the end of the year. The biotech is also preparing to analyze top-line data on around 20 patients with Type 1 diabetes who enrolled in a phase 2a study. Neither timeline was “materially impacted” by the clinical hold, Butler said. The CEO said the data will help confirm the optimal dosing scheme to inform planned phase 3 studies.
The biotech is preparing to move BMF-219 into phase 3 in the belief the molecule can fill a gap in the diabetes treatment arsenal. BMF-219 targets beta cells to improve glycemic control. Frías believes the mechanism differentiates BMF-219 from existing diabetes drugs.
“It is an oral small molecule with a mechanism of action that is complementary to today's agents, including GLP-1 receptor agonist-based therapy and SGLT2 inhibitors,” Frías said. “Importantly, we believe that it may not require chronic dosing given its mechanism of action and the lifespan of a beta cell, which is measured in the order of decades.”
Shares in Biomea rose 9% to $9.57 after the FDA lifted the hold. The stock traded above $11 before the FDA imposed the hold but crashed to around $4 in the immediate aftermath of the regulatory action.