Johnson & Johnson's First-in-Class Menin Inhibitor Bleximenib Granted IND Approval in China for Relapsed/Refractory AML

Sep 19, 2024 16:13 CST Updated 16:13

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Today (September 19), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has just announced,Johnson & Johnson's申报的1类新药bleximenib胶囊获批临床，拟用于治疗携带组蛋白-赖氨酸N-甲基转移酶2A重排（KMT2Ar) or nucleophosmin 1 gene mutation (NPM1m) ofAdult patients with relapsed/refractory acute myeloid leukemia (AML)。Public information shows that bleximenib is aMenin-KMT2A Interaction Inhibitor, and is currently conducting Phase 1/2 clinical trials internationally.According to the CDE official website, this is the first IND approval for the product in China.

Image Source:CDE Official Website

Research shows,KMT2AGene Rearrangement andNPM1Gene mutations can lead to the degeneration or dedifferentiation of blood cells, causing them to behave like the stem cells they originated from, resulting in arrested hematopoietic differentiation and leukemic transformation.And this process depends onMEN1Menin Protein Encoded by Genes. BaseDeveloped for the Menin-KMT2A InteractionMenin InhibitorIt is considered a promising new therapy for treating leukemia, especially for those carryingKMT2AGene Rearrangement orNPM1AML Patients with Gene Mutations。

Bleximenib (JNJ-75276617) is a potent, selective Menin-KMT2A interaction inhibitor. Preclinical studies have shown that this product has a unique binding mode with menin, distinguishing it from other similar products. According toClinicalTrialsOfficial website, the product is currently in 1/Phase 2 Clinical Research Stage,As a monotherapy or in combination with other targeted therapies for the treatment of acute leukemia。

At the EHA Annual Meeting held in June 2024, researchers reportedbleximenibCombination of venetoclax and azacitidine for the treatment ofKMT2AReorganization orNPM1Relapsed/Refractory Acute Myeloid Leukemia with MutationsResults of Phase 1b Study.Safety data showed that 87% (39/45) of patients experienced at least one TRAE, with nausea, vomiting, and thrombocytopenia being the most common. Grade ≥3 TRAEs were observed in 60% of patients, and TRAEs solely attributed to JNJ-75276617 were observed in 22% of patients.To date, no reports of differentiation syndrome (DS), QTcF prolongation,Tumor Lysis Syndrome (TLS) andDose-Limiting Toxicity (DLT)。

InbleximenibIn the efficacy data set with a BID dose level of 50mg,Objective Response Rate（ORR (≥PR) was 86% (18/21), CR/CRh/CRi (i.e., cCR) rate was 48%, and the CR/CRh rate was 24%. For patients previously exposed to VEN,ORR was 82%The cCR rate was 36%, and the CR/CRh rate was 18%. The median time to first response in the efficacy dataset was 23 days, and the median time to cCR was 52 days. Among all dose-escalation cohorts (n=45), 9 responders discontinued treatment and proceeded to allogeneic transplantation, while another 11 patients remain on active treatment, including one patient who has been receiving study treatment for over 12 months.

In addition, in 2023, Johnson & Johnson also published in international journalsBloodPublished onbleximenibMonotherapyKMT2AOrNPM1Adult patients with relapsed/refractory acute leukemia harboring mutationsResults of the first-in-human Phase 1 study.The study suggests that,bleximenibMonotherapy has acceptable safety and encouraging anti-leukemia activity.. In September this year, the preclinical research results of this product were published again inBloodMagazine.

This time, this productMenin-KMT2A Inhibitor Approved for Clinical Trials in China, Signaling the Start of Clinical Research in the Country.

References:

[1] Website of the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) of China. Retrieved Sep 19, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2]]A First-in-Human Phase 1 Study of the Menin-KMT2A (MLL1) Inhibitor JNJ-75276617 in Adult Patients with Relapsed/Refractory Acute Leukemia Harboring KMT2A or NPM1 Alterations. Retrieved Nov 2, 2023, from https://ashpublications.org/blood/article/142/Supplement%201/57/499087/A-First-in-Human-Phase-1-Study-of-the-Menin-KMT2A

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