Biomea Fusion announced positive 52-week results from its Phase II COVALENT-111 study, demonstrating that icovamenib, an investigational menin inhibitor, provides sustained glycemic benefits in type 2 diabetes patients nine months after treatment completion. The findings represent a potential paradigm shift in diabetes care, offering durable effects from a finite treatment course rather than chronic therapy.
Sustained Benefits in Severe Insulin-Deficient Patients
The study's most compelling results emerged in severe insulin-deficient diabetes patients, a population characterized by impaired insulin secretion, the lowest beta cell function among type 2 diabetes subtypes, and rapid disease progression. Among patients who received 12 weeks of treatment (n=10), icovamenib achieved a durable HbA1c reduction of 1.2% (p=0.01) sustained through Week 52.
The strongest performing treatment arm was Arm B, where six patients received 100mg once daily for 12 weeks, achieving a mean HbA1c reduction of 1.5% (p=0.01). This population was prospectively defined prior to unblinding using the Ahlqvist algorithm and represents patients with substantial unmet medical need.
"The 52-week durability in severe insulin-deficient patients is remarkable. These are the most difficult to treat patients, and no current therapy provides this kind of lasting benefit for them without chronic dosing," said Professor Ralph DeFronzo, M.D., University of Texas Health Science Center. "The HbA1c reductions we are seeing in this study readout, sustained long after the treatment had stopped, suggest a restoration of beta cell function."
Enhanced GLP-1 Therapy Response
The study also revealed clinically meaningful benefits in patients receiving GLP-1-based therapy who had not achieved glycemic targets at study entry. In this subgroup of 11 patients across all treatment arms, 8 or 12 weeks of icovamenib resulted in a 1.3% reduction in HbA1c (p=0.05) with effects sustained through Week 52.
DeFronzo noted the "interplay with GLP-1 based agents, whereby icovamenib seems to have given renewed impact to these agents," suggesting potential combination therapy applications.
Study Design and Safety Profile
COVALENT-111 is a double-blind, randomized, placebo-controlled trial that enrolled adult patients diagnosed with type 2 diabetes within the last seven years. Eligible participants had HbA1c levels between 7.0% and 10.5%, and a body mass index between 25 and 40 kg/m². The study evaluated three dosing regimens: 100mg once daily for 8 weeks (Arm A), 100mg once daily for 12 weeks (Arm B), and 100mg once daily for 8 weeks followed by 100mg twice daily for 4 weeks (Arm C).
A total of 267 patients received at least one dose of icovamenib. The efficacy analysis included 163 patients who completed at least 80% of their planned dosing prior to a temporary FDA clinical hold and were treated with one or more antihyperglycemic agents at baseline.
Icovamenib maintained a favorable safety profile throughout the 52-week observation period, with no treatment-related serious adverse events or discontinuations due to adverse events. The drug was generally well tolerated across all dosing arms.
Mechanism of Action and Clinical Significance
Icovamenib is an orally bioavailable, potent, and selective covalent inhibitor of menin, a regulator of beta cell quantity and function. The proposed mechanism involves selective and partial inhibition of menin, enabling the proliferation, preservation, and reactivation of patients' own healthy, functional, insulin-producing beta cells.
Loss of functional beta cell mass is a core component of both type 1 and type 2 diabetes progression. Menin is thought to act as a brake on beta cell turnover and growth, supporting the rationale that menin inhibition could lead to regeneration of normal, healthy beta cells.
"I believe icovamenib represents a major advancement, with the potential to become a new pillar of diabetes care as it addresses the root cause of diabetes, the dysfunction of beta cells," DeFronzo stated.
Development Pipeline and Next Steps
Biomea Fusion has outlined an aggressive development timeline for icovamenib. The ongoing Food Effect Study (COVALENT-121) is expected to be completed by December 2025 to optimize dosing criteria. Two Phase II trials are planned for initiation in the fourth quarter of 2025: COVALENT-211 in severe insulin-deficient type 2 diabetes patients and COVALENT-212 combining icovamenib with GLP-1-based therapy.
The company is also advancing BMF-650, an oral GLP-1 receptor agonist, with a Phase I trial (GLP-131) in obese, otherwise healthy volunteers ongoing and data anticipated in the first half of 2026.
"We believe that we now have in hand initial evidence of durable efficacy, additional favorable safety data, a clear understanding of an effective dose, and most importantly, the target patient populations," said Mick Hitchcock, Ph.D., Interim CEO and Board Member of Biomea Fusion. "Icovamenib demonstrates potential to transform the diabetes treatment landscape by effectively addressing the underlying biology."
Market Context
The diabetes burden continues to expand, with the Centers for Disease Control and Prevention estimating that about two in five adults in the United States are expected to develop diabetes during their lifetime. More than 38 million people of all ages have diabetes today, representing about 11% of the US population. Diabetes accounts for one out of every four dollars in US healthcare spending.
Severe insulin-deficient diabetes patients represent a particularly challenging population, often presenting with higher HbA1c levels at diagnosis, lower body mass index compared to insulin-resistant patients, and rapid decline in beta cell function. This group has the highest risk of complications such as retinopathy and neuropathy and typically progresses fastest to insulin therapy.
