On October 6, 2025, Biomea Fusion, Inc. (the “Company”) reported new 52-week results from Phase II COVALENT-111 study in Type 2 diabetes.
COVALENT-111 Study Design and Results
COVALENT-111 is a double-blind, randomized, placebo-controlled trial that enrolled adult patients diagnosed with type 2 diabetes (“T2D”) within the last 7 years. Eligible participants had HbA1c levels between 7.0% and 10.5%, and a body mass index (BMI) between 25 and 40 kg/m². At baseline, all participants were treated with lifestyle management, including diet and exercise, with or without antidiabetic medications and had inadequate glycemic control despite treatment with up to three antidiabetic medications.
The study evaluated icovamenib in three dosing regimens: Arm A at 100mg QD (once daily) for 8 weeks, Arm B at 100mg QD for 12 weeks, and Arm C at 100 mg QD for 8 weeks and 100mg BID (twice daily) for 4 weeks. A total of 267 patients received at least one dose of icovamenib and were considered evaluable for the modified intent-to-treat (“mITT”) population. As previously reported, dosing was interrupted an interim clinical hold imposed by the U.S. Food and Drug Administration (“FDA”). The topline efficacy analysis presented here includes the patient population (N=163) who had completed at least 80% of their planned dosing prior to the clinical hold (without other significant protocol deviations) and who, at baseline, were treated with one or more antihyperglycemic agents. As prespecified in the statistical analysis plan, outcomes were prospectively evaluated by diabetes phenotype using the Ahlqvist algorithm.
The study showed positive results, while exploratory, through Week 52 across multiple subgroups, with certain groups demonstrating statistically significant and clinically meaningful reductions in HbA1c, the gold standard for assessing glycemic control in T2D, observed nine months after dosing. In the 26-week analysis, 8 weeks of dosing was found to be less effective than 12. Accordingly, the 52-week readout primarily focused on patients in Arms B and C who received 12 weeks of treatment (n=10). Among these severe insulin-deficient patients, icovamenib achieved a durable HbA1c reduction of 1.2% (p=0.01) sustained through Week 52. The strongest performing arm for this prespecified population was Arm B (n=6; 100mg QD for 12 weeks), with a mean HbA1c reduction of 1.5% (p=0.01). Severe insulin-deficient diabetes is characterized by impaired insulin secretion, the lowest beta cell function among T2D subtypes, and rapid disease progression. This group was prospectively defined prior to unblinding and represents a population with substantial unmet need.
The 52-week analysis also showed clinically meaningful benefit in study participants who were receiving a GLP-1-based therapy but had not achieved glycemic targets at study entry (all arms n=11). In this subgroup, 8 or 12 weeks of icovamenib resulted in a 1.3% reduction in HbA1c (p=0.05) with effects sustained through Week 52.
Icovamenib maintained a favorable safety profile throughout the 52-week observation period. There were no treatment-related serious adverse events or discontinuations due to adverse events. Across all dosing arms, icovamenib was generally well tolerated.
Planned Next Steps
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Food Effect Study (COVALENT-121) is ongoing, to optimize the dosing criteria for icovamenib, and expected to be completed by December 2025 |
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Phase IIb trial (COVALENT-211) in severe insulin-deficient type 2 diabetes patients, is expected to be initiated in the fourth quarter of 2025 |
