Biomea Fusion presented new data at the 1st Annual Asian Conference on Innovative Therapies for Diabetes Management (ATTD-ASIA 2024) indicating that icovamenib, an oral menin inhibitor, shows promise in treating type 2 diabetes (T2D) patients characterized by insulin deficiency. The analysis, derived from the escalation portion of the COVALENT-111 trial, reveals a clinically significant reduction in HbA1c levels in this patient subgroup.
The data, presented on November 19, 2024, highlighted that 83% of insulin-deficient patients responded to icovamenib, exhibiting a mean HbA1c reduction of 1.23% compared to baseline, placebo-adjusted, 22 weeks after the last dose. In contrast, patients identified as insulin-resistant showed a smaller reduction of 0.48%. This suggests that icovamenib may offer a targeted therapeutic approach for the severe insulin-deficient diabetes (SIDD) and mild age-related diabetes (MARD) subgroups, which constitute a significant portion of T2D patients.
Detailed Findings from COVALENT-111
The analysis included 32 patients from the 100mg and 200mg cohorts of the COVALENT-111 trial, doses selected for the expansion phase. These patients were characterized based on baseline biomarkers and analyzed for efficacy. The study compared the mean reduction in HbA1c at Week 26, following 4 weeks of dosing, between insulin-deficient and insulin-resistant patients.
Two case studies were presented to further illustrate the potential of icovamenib in poorly controlled, insulin-deficient T2D patients. In one case, a 29-year-old male with a four-year history of T2D experienced a 2.5% reduction in HbA1c at Week 26, which further decreased by 1.2% at Week 47, leading to the discontinuation of metformin. Both HOMA-B (+190.0%) and C-peptide (+71.0%) levels increased significantly during the study period. Another patient, a 45-year-old male with a 10-year history of T2D, showed a 1.1% reduction in HbA1c at Week 26, with notable increases in HOMA-B (+1233.0%) and C-peptide (+59.0%).
COVALENT-111 and COVALENT-112 Trials
COVALENT-111 is a Phase I/II trial evaluating the safety and efficacy of icovamenib in adults with T2D. The expansion portion of the trial involves dosing patients for up to 12 weeks, with follow-up at Weeks 26 and 52, to identify the optimal dose for late-stage development and define biomarkers for patient selection. Key inclusion criteria include T2D patients with HbA1c greater than 7.0%, a BMI of 25 to 40, diabetes onset within the last seven years, and failure of current treatments.
COVALENT-112 is a Phase II trial assessing icovamenib in adults with stage three type 1 diabetes (T1D). The open-label portion of the study examines the efficacy, safety, and durability of icovamenib at 100 mg and 200 mg doses over a 12-week treatment period, followed by a 40-week off-treatment period.
Future Directions
Biomea Fusion anticipates topline results from the Phase IIb expansion portion of COVALENT-111 in December. These results are expected to provide critical insights into how icovamenib affects both insulin-deficient and insulin-resistant patients, aiding in the identification of biomarkers for optimal patient selection. The company aims to discuss these findings with the FDA in a potential end-of-Phase II meeting in 2025.
According to Juan Pablo Frias, MD, Biomea Fusion’s Chief Medical Officer, the company is excited about icovamenib’s potential and looks forward to reporting the study results, emphasizing the overall benefit it may provide, particularly to insulin-deficient patients with T2D.
