Biomea Fusion Announces Positive Topline Results from Ongoing Phase II COVALENT-111 Study in Patients with Type 2 Diabetes
Biomea Fusion (BMEA) announced positive topline results from its Phase II COVALENT-111 study evaluating icovamenib in type 2 diabetes patients. The study met its primary endpoint, showing statistically significant HbA1c reductions across all major categories. The most significant results were observed in insulin-deficient patients, with a placebo-adjusted mean reduction of 1.47% in HbA1c at Week 26 in the severe insulin-deficient diabetes (SIDD) group.
The study enrolled 225 patients, with 168 completing the per-protocol analysis. The optimal dosing was identified as 100mg once daily for 12 weeks, showing a mean HbA1c reduction of 0.5%. Notably, the drug demonstrated efficacy in patients who failed GLP-1 based therapy, achieving an HbA1c reduction of 0.84%. The treatment was well-tolerated with no serious adverse events or discontinuations due to adverse events.
Biomea Fusion (BMEA) ha annunciato risultati positivi preliminari del suo studio di Fase II COVALENT-111 che valuta icovamenib in pazienti con diabete di tipo 2. Lo studio ha raggiunto il suo obiettivo primario, mostrando riduzioni statisticamente significative dell'HbA1c in tutte le principali categorie. I risultati più significativi sono stati osservati nei pazienti con carenza di insulina, con una riduzione media corretta rispetto al placebo dell'1,47% dell'HbA1c alla settimana 26 nel gruppo di diabete severamente insulinodipendente (SIDD).
Lo studio ha arruolato 225 pazienti, di cui 168 hanno completato l'analisi per protocollo. Il dosaggio ottimale è stato identificato in 100 mg una volta al giorno per 12 settimane, mostrando una riduzione media dell'HbA1c dello 0,5%. È interessante notare che il farmaco ha dimostrato efficacia in pazienti che non hanno risposto alla terapia basata su GLP-1, ottenendo una riduzione dell'HbA1c dello 0,84%. Il trattamento è stato ben tollerato senza eventi avversi gravi o interruzioni dovute a eventi avversi.
Biomea Fusion (BMEA) anunció resultados positivos preliminares de su estudio de Fase II COVALENT-111 que evalúa icovamenib en pacientes con diabetes tipo 2. El estudio cumplió con su objetivo primario, mostrando reducciones estadísticamente significativas en HbA1c en todas las categorías principales. Los resultados más significativos se observaron en pacientes con deficiencia de insulina, con una reducción media ajustada por placebo del 1.47% en HbA1c en la semana 26 en el grupo de diabetes severamente deficiente en insulina (SIDD).
El estudio incluyó 225 pacientes, de los cuales 168 completaron el análisis por protocolo. La dosis óptima se identificó como 100 mg una vez al día durante 12 semanas, mostrando una reducción media del HbA1c del 0.5%. Es notable que el medicamento demostró eficacia en pacientes que no respondieron a la terapia basada en GLP-1, logrando una reducción de HbA1c del 0.84%. El tratamiento fue bien tolerado sin eventos adversos graves ni interrupciones debidas a eventos adversos.
Biomea Fusion (BMEA)는 제2형 당뇨병 환자를 대상으로 한 icovamenib의 2상 COVALENT-111 연구에서 긍정적인 주요 결과를 발표했습니다. 이 연구는 주요 목표를 달성하였으며, 모든 주요 범주에서 통계적으로 유의미한 HbA1c 감소를 나타냈습니다. 가장 중요한 결과는 인슐린 결핍 환자에서 관찰되었으며, 심각한 인슐린 결핍 당뇨병(SIDD) 그룹에서 26주차에 HbA1c의 평균 감소가 플라시보 조정으로 1.47%에 달했습니다.
이 연구는 225명의 환자를 등록하였고, 그 중 168명이 프로토콜 분석을 완료했습니다. 최적 용량은 12주 동안 하루 100mg으로 확인되었으며, HbA1c의 평균 감소는 0.5%였습니다. 주목할 점은 이 약물이 GLP-1 기반 치료에 실패한 환자들에서 효능을 나타냈으며, HbA1c가 0.84% 감소했습니다. 치료는 잘 견디며 심각한 부작용이나 부작용으로 인한 중단은 없었습니다.
Biomea Fusion (BMEA) a annoncé des résultats préliminaires positifs de son étude de Phase II COVALENT-111 évaluant icovamenib chez des patients atteints de diabète de type 2. L'étude a atteint son objectif principal, montrant des réductions HbA1c statistiquement significatives dans toutes les catégories principales. Les résultats les plus significatifs ont été observés chez les patients déficients en insuline, avec une réduction moyenne corrigée par rapport au placebo de 1,47 % de l'HbA1c à la semaine 26 dans le groupe de diabète sévèrement déficient en insuline (SIDD).
L'étude a inclus 225 patients, dont 168 ont complété l'analyse selon le protocole. La posologie optimale a été identifiée à 100 mg une fois par jour pendant 12 semaines, montrant une réduction moyenne de l'HbA1c de 0,5 %. Notamment, le médicament a démontré son efficacité chez les patients n'ayant pas répondu à un traitement basé sur le GLP-1, atteignant une réduction de l'HbA1c de 0,84 %. Le traitement a été bien toléré, sans événements indésirables graves ni interruptions dues à des événements indésirables.
Biomea Fusion (BMEA) hat positive vorläufige Ergebnisse aus seiner Phase-II-Studie COVALENT-111 veröffentlicht, die icovamenib bei Patienten mit Typ-2-Diabetes bewertet. Die Studie erreichte ihr primäres Ziel und zeigte statistisch signifikante HbA1c-Reduzierungen in allen wichtigen Kategorien. Die signifikantesten Ergebnisse wurden bei insulinmangelnden Patienten beobachtet, mit einer placebo-korrigierten durchschnittlichen Reduktion von 1,47 % HbA1c in der 26. Woche in der Gruppe mit schwerem Insulinmangel-Diabetes (SIDD).
In der Studie wurden 225 Patienten eingeschlossen, von denen 168 die protokollgerechte Analyse abgeschlossen haben. Die optimale Dosierung wurde als 100 mg einmal täglich für 12 Wochen identifiziert, was eine durchschnittliche HbA1c-Reduzierung von 0,5 % zeigte. Bemerkenswert ist, dass das Medikament bei Patienten, die auf eine GLP-1-basierte Therapie nicht angesprochen hatten, eine HbA1c-Reduzierung von 0,84 % erreichte. Die Behandlung wurde gut vertragen, ohne schwerwiegende unerwünschte Ereignisse oder Abbrüche aufgrund unerwünschter Ereignisse.
- Met primary endpoint with statistically significant HbA1c reductions
- Strong efficacy in insulin-deficient patients (1.47% HbA1c reduction)
- Effective in GLP-1 therapy failure patients (0.84% HbA1c reduction)
- Clean safety profile with no serious adverse events
- No drug-to-drug interactions observed
- Study disrupted by FDA clinical hold
- COVALENT-112 study in type 1 diabetes impacted with 90% incomplete dosing
Insights
The Phase II COVALENT-111 study results represent a significant breakthrough in T2D treatment. The study's primary endpoint was met with icovamenib showing a statistically significant placebo-adjusted mean HbA1c reduction of
The identification of optimal patient populations - MARD and SIDD subtypes representing over
These positive Phase II results significantly de-risk Biomea Fusion's lead program and validate their covalent small molecule platform. The clear identification of responsive patient populations (MARD and SIDD) and optimal dosing regimen (100mg QD for 12 weeks) provides a well-defined path to market. The drug's efficacy in GLP-1 failures is particularly noteworthy, as it could position icovamenib as a valuable alternative in a growing market segment.
The planned FDA engagement following the 52-week readout in H2 2025 could accelerate the development timeline. However, investors should note the ongoing clinical hold implications and the need for additional data from the COVALENT-112 study in type 1 diabetes. The market opportunity is substantial, given the large addressable patient population and unique mechanism of action.
- Icovamenib met the primary endpoint, displaying a meaningful statistically significant placebo-corrected mean reduction in HbA1c in the prespecified per protocol patient population
- Best response achieved in target, beta-cell deficient patients on one or more antidiabetic agents at baseline, showing a placebo-adjusted mean reduction of
1.47% in HbA1c at Week 26 with statistical significance, after only 12 weeks of dosing icovamenib with 100 mg - Icovamenib was well-tolerated, with no adverse-event related discontinuations, no hypoglycemic events and no serious adverse events
REDWOOD CITY, Calif., Dec. 17, 2024 (GLOBE NEWSWIRE) -- Biomea Fusion, Inc. (“Biomea” or “Biomea Fusion” or “the Company”) (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers, today 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).
COVALENT-111 is a double-blinded, randomized, 3:1 placebo-controlled trial that has enrolled adult patients diagnosed with T2D within the last 7 years, who had HbA1c levels between
The study showed positive topline results at Week 26, demonstrating statistically significant and clinically meaningful reductions in HbA1c, the gold standard for assessing glycemic control in T2D. In patients who completed dosing per protocol and were suboptimally controlled at baseline on one or more prior agent, icovamenib showed meaningful reductions in HbA1c with statistical significance in all major categories. Here icovamenib showed a mean reduction in HbA1c of
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.
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
The study will further assess secondary endpoints (e.g., HbA1c reduction, fasting glucose, HOMA-B and HOMA-IR) within each pre-specified subtype to identify distinct patterns of response. 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.
"I am very excited about these initial results we are presenting today. We believe we now have a defined path to further develop icovamenib in diabetes. We have identified the optimal dose, the patient population to target, and most importantly, we now have strong efficacy and safety data," says Thomas Butler, CEO and Chair of Biomea Fusion. "These results validate our approach and highlight that icovamenib has the potential to address an aspect of diabetes that no other current therapy can. We are excited to continue advancing this promising molecule and bring a new treatment option to patients who need it most."
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.
Conference Call and Webcast Details
Webcast of Biomea’s investor update on Tuesday, December 17, 2024, at 8:00 am EST will be available to registered attendees under the Investors and Media section of the company’s website at https://investors.biomeafusion.com/news-events/events. A replay of the presentation will be archived on Biomea’s site following the event.
The clinical hold which was placed on icovamenib was due to data FDA had observed during the Escalation Phase, when higher dosages of icovamenib were tested. The clinical hold led to a disruption for patients enrolled in the COVALENT-111 study. It had a more profound impact on the ongoing Phase II COVALENT -112 study in type 1 diabetes, where over
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.
About Menin’s Role in Diabetes
Loss of functional beta cell mass is a core component of the natural history in both types of diabetes — type 1 diabetes (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 notion that inhibition of menin could lead to the regeneration of normal, healthy beta cells. Based on these and other scientific findings, Biomea is exploring the potential for icovamenib-mediated menin inhibition as a viable therapeutic approach to potentially halt or reverse progression of T2D.
About Type 2 Diabetes
Diabetes is considered a chronic health condition that affects how the body turns food into energy and results in excessive glucose in the bloodstream. Over time, this can cause serious health problems and damage vital organs. Most people with diabetes have a shorter life expectancy than people without this disease. The Centers for Disease Control and Prevention estimates about two in five adults in the United States are now expected to develop diabetes during their lifetime. More than 37 million people of all ages (about
About Biomea Fusion
Biomea Fusion is a clinical-stage biopharmaceutical company focused on the discovery and development of oral covalent small molecules to improve the lives of patients with diabetes, obesity, and genetically defined cancers. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response.
We are utilizing our proprietary FUSION™ System to discover, design and develop a pipeline of next-generation covalent-binding small-molecule medicines designed to maximize clinical benefit for patients. We aim to have an outsized impact on the treatment of disease for the patients we serve. We aim to cure.
Visit us at biomeafusion.com and follow us on LinkedIn, X, and Facebook.
Forward-Looking Statements
Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our product candidates and development programs, their mechanism of action, and their potential relative to approved products marketed by third parties; the potential benefits to future trial design and program development of subtyping diabetes patients; our research, development and regulatory plans, the progress of our ongoing and upcoming clinical trials and the timing of such events may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that preliminary or interim results of preclinical studies or clinical trials may not be predictive of future or final results in connection with future clinical trials that our analysis of preliminary or interim data in subsets of patients may not be predictive of our product candidate in a broader patient population, and the risk that we may encounter delays in preclinical or clinical development, patient enrollment and in the initiation, conduct and completion of our ongoing and planned clinical trials and other research and development activities. These risks concerning Biomea Fusion’s business and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission (SEC), including its most recent periodic report filed with the SEC and subsequent filings thereafter. Biomea Fusion explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
Contact:
Ramses Erdtmann
COO & President of Biomea Fusion
re@biomeafusion.com
FAQ
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