Announcement • Apr 29
Biomea Fusion, Inc. Announces Positive 52-Week Results from Phase 2 COVALENT-112 Trial in Type 1 Diabetes Showing C-Peptide Improvement and Durability Following 12-Weeks of Icovamenib Treatment
Biomea Fusion, Inc. had announced positive 52-week results from its Phase 2 COVALENT-112 trial evaluating the efficacy, safety, and tolerability of icovamenib in patients with type 1 diabetes (“T1D”). These data are based on a proof-of-concept study enrolling small subsets of Stage 3 T1D patients dosed with icovamenib at 100 mg and 200 mg in two cohorts (patients diagnosed within 3 years and those diagnosed within 3-15 years). The COVALENT-112 trial demonstrated encouraging results in patients with T1D. In patients diagnosed within 0-3 years, treatment with icovamenib 200 mg once daily for 12 weeks resulted in a 52% increase in mean C-peptide area under the curve (AUC) at Week 12 (p < 0.001; n=5), representing a magnitude of improvement that is not commonly reported in published studies of T1D. The effect was durable following only 12 weeks of dosing, mean C-peptide AUC was largely preserved through Week 52, representing approximately a 7% decline from baseline. A dose response was observed, with the 200 mg dose demonstrating greater activity compared to 100 mg. Published natural history data suggest that patients with Stage 3 T1D typically experience substantial declines in C-peptide over time, underscoring the significance of preserved C-peptide following only a 12-week dosing period. In patients with longer-standing disease (3-15 years since diagnosis), C-peptide levels were generally preserved through Week 52 (12-week treatment period + 40-week follow-up), with only a modest decline from baseline. Icovamenib was generally well tolerated, with no new or unexpected safety signals identified throughout the 52-week observation period. Unlike investigational approaches in T1D that rely primarily on immune suppression or cellular transplantation, icovamenib is designed as a short course, orally administered therapy targeting beta cell biology, with effects that appear to persist beyond the treatment period. Based on these data, Biomea, in collaboration with four U.S. academic centers, is planning a Phase 2 trial in patients with T1D diagnosed within the past 3 years. The study will evaluate whether extended dosing (up to 6 or 12 months) at 200 mg further improves C-peptide and whether the addition of an immunosuppressive agent enhances clinical outcomes. This study is planned to be initiated within the second half of this year at the Barbara Davis Center for Diabetes, Joslin Diabetes Center, UT Health San Antonio Diabetes Center, and the University of Miami Diabetes Research Institute. COVALENT-112 (NCT06152042) was an open label Phase 2 trial evaluating icovamenib in adult patients with T1D. The study enrolled patients aged 18 to 60 years with Stage 3 T1D, including those diagnosed within 0–3 years with residual beta cell function at baseline, defined by a screening C-peptide level =0.2 nmol/L (Cohort 1), as well as a broader population with disease duration of 3–15 years and residual beta cell function at baseline, defined by a screening C-peptide level =0.08 nmol/L (Cohort 2). Participants were assigned to receive icovamenib at 100 mg or 200 mg once daily for 12 weeks, followed by a 40-week post-treatment follow-up to assess durability of effect. Study enrollment and dosing were interrupted in May 2024 due to an FDA clinical hold, which was subsequently resolved. As a result, these data reflect approximately half of the originally intended patient population. A planned placebo-controlled Part 2 of the study was not completed. The primary endpoint was the mean change from baseline in stimulated C-peptide area under the curve (AUC), measured during a mixed-meal tolerance test (MMTT), to evaluate endogenous insulin secretion. Secondary endpoints included additional measures of beta cell function, glycemic control, insulin use, and safety. Icovamenib is an orally administered investigational small molecule currently in Phase 2 clinical development for the treatment of diabetes. Icovamenib targets menin, a transcriptional regulator implicated in beta cell dysfunction, and has been shown in preclinical and clinical studies to induce transient reductions in menin protein levels in pancreatic islets, thereby modulating pathways associated with insulin secretion and glycemic control. Through this mechanism, icovamenib has the potential to restore beta cell mass and function and improve endogenous insulin production. As a potential short-course therapy, icovamenib could represent a novel treatment approach for patients with diabetes, particularly those who have not achieved adequate control with standard-of-care therapies. Loss of functional beta cell mass is a core component of the natural history in both major types of diabetes, T1D (mediated by autoimmune dysfunction) and T2D (mediated by metabolic dysfunction). Beta cells are found in the pancreas and are responsible for the synthesis and secretion of insulin. Insulin is a hormone that helps the body use glucose for energy and helps control blood glucose levels. In patients with diabetes, beta cell mass and function have been observed to be diminished, leading to insufficient insulin secretion and hyperglycemia. Menin is thought to act as a brake on beta cell turnover and growth, supporting the hypothesis that inhibition of menin may enable pathways associated with beta cell regeneration and improved function. Based on these and other scientific findings, Biomea is exploring the potential for icovamenib-mediated menin inhibition as a viable therapeutic approach to treat T1D and T2D. Type 1 diabetes (T1D) is a chronic autoimmune disease in which the body’s immune system destroys insulin-producing beta cells in the pancreas, leading to a loss of endogenous insulin production. Approximately 9,500,000 people worldwide live with T1D, with an estimated 513,000 new diagnoses each year. In the United States, about 1,800,000 individuals are affected. At diagnosis, patients often have already lost a significant portion of their functional beta cell mass, and this decline typically continues over time. As a result, individuals with T1D require lifelong insulin therapy and continuous glucose monitoring to manage blood sugar levels. Despite advances in care, T1D remains associated with meaningful risks, including severe hypoglycemia and diabetic ketoacidosis (DKA), as well as long-term complications such as cardiovascular disease, kidney disease, nerve damage, and vision loss. There are currently no approved therapies that address the underlying progressive loss of beta cell function in established (Stage 3) T1D beyond insulin replacement, highlighting a significant unmet medical need for disease-modifying treatments.
