Biomea Fusion announced positive topline results from the ongoing COVALENT-111 study, evaluating the efficacy, safety, and tolerability of icovamenib in patients with type 2 diabetes (T2D). The Phase II trial demonstrated statistically significant and clinically meaningful reductions in HbA1c, the gold standard for assessing glycemic control in T2D.
The COVALENT-111 trial is a double-blinded, randomized, 3:1 placebo-controlled study that enrolled adult patients diagnosed with T2D within the last 7 years, who had HbA1c levels between 7.0% and 10.5%, and a body mass index (BMI) between 25 and 40 kg/m². Participants were receiving treatment with diet and exercise and were uncontrolled with up to three antidiabetic medications at baseline. Icovamenib was investigated in three different dosing arms: 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. The study enrolled a total of 225 patients.
Significant HbA1c Reduction
The study demonstrated a mean reduction in HbA1c of 0.36% (p=0.022) in patients who completed dosing per protocol and were suboptimally controlled at baseline on one or more prior agent. The strongest performing arm was Arm B (icovamenib dosed at 100mg QD for 12 weeks) with a mean HbA1c reduction of 0.5% (p=0.012).
In the analysis of the T2D phenotypes, icovamenib showed further improved reduction in the insulin deficient patients. Within the mild age-related diabetes (MARD) and severe insulin-deficient diabetes (SIDD) patients the mean HbA1c reduction was 0.73% (p=0.009) and in Arm B these patient subtypes reduced the mean HbA1c by 1.05% (p=0.004). Patients who were considered most severe insulin deficient, the SIDDs, demonstrated the best response with a mean HbA1c reduction in Arm B of 1.47% (p=0.022).
Safety and Tolerability
Throughout the 26-week period, there were no serious adverse events or discontinuations due to adverse events observed. No drug-to-drug interactions were observed during the study. Overall, icovamenib was well tolerated and demonstrated a favorable safety profile in the COVALENT-111 study.
Patient Subtypes
The company used clinical biomarker data to categorize participants into prespecified subtypes (SIDD, MARD, SIRD, and MOD) during screening:
- SIDD: Characterized by low insulin secretion, high HbA1c, and reduced beta-cell function (low HOMA-B)
- MARD: Characterized by mild age-related diabetes, typically older age at onset, with mild hyperglycemia and fewer metabolic disturbances
- SIRD: Defined by significant insulin resistance, high HOMA-IR, and potential complications like liver disease
- MOD: Identified by mild obesity, less severe insulin resistance, and relatively mild hyperglycemia
Future Plans
Analysis of the full Phase II COVALENT-111 data is ongoing and Biomea Fusion plans to present detailed results at an upcoming medical conference in 2025. Based on these initial results and the upcoming 52-week readout in the second half 2025, Biomea plans to engage with the FDA to discuss the data. This meeting will provide an opportunity to align with FDA on how to further advance icovamenib as a first-in-class menin inhibitor therapy for T2D.
"The topline data from the COVALENT-111 Phase II study are incredibly promising, showing that icovamenib delivers significant and clinically meaningful reductions in HbA1c. We now understand the duration of dosing and target patient population. This study confirms the potential of menin inhibition as a novel mechanism for treating type 2 diabetes. Achieving a HbA1c reduction of this magnitude without chronic treatment is paradigm shifting in diabetes therapy," said Dr. Juan Pablo Frias, Chief Medical Officer of Biomea Fusion.
About Icovamenib
Icovamenib is an investigational, orally bioavailable, potent, and selective covalent inhibitor of menin. The molecule was built using Biomea Fusion’s FUSION™ System and is designed to regenerate insulin-producing beta cells with the aim to cure diabetes. Icovamenib’s proposed mechanism of action in diabetes is to enable the proliferation, preservation, and reactivation of a patient’s own healthy, functional, insulin-producing beta cells. As the potentially first disease-modifying therapy for T1D and T2D, icovamenib could become an important addition and complement to the diabetes treatment landscape once it has successfully completed its ongoing clinical studies.
