Merck's LSD1 Inhibitor Bomedemstat Granted Clinical Trial Approval in China for Essential Thrombocythemia

Jun 18, 2024 16:00 CST Updated 16:00

MSD

Pharmaceutical R&D and Manufacturer

On June 17, 2024, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,MSD's Class 1 new drug, bomedemstat capsule, has been approved for clinical trials and is proposed for development to treatPrimary Thrombocythemia. Publicly available information shows that bomedemstat (MK-3543) is aOral Lysine-Specific Demethylase 1 (LSD1) InhibitorIn November 2022, MSD spent approximately US$1.35 billion in cashAcquisitionImago, thereby acquiring the latter's main candidate drug, which is currently in Phase 2 clinical stage. The product is currently in Phase 3 clinical stage internationally.

Screenshot source: CDE official website

LSD1 is an epigenetic regulatory protein that regulates the maturation of bone marrow stem cells and is crucial for the self-renewal of hematopoietic stem cells and the maturation of progenitor cells. This protein also plays a significant role in many hematological malignancies and is considered one of the emerging targets for treating various high-mortality blood cancers.

According to the public information from MSD, in non-clinical studies, bomedemstat was used both as a single agent and in combination with other therapeutic agents.Demonstrated potent in vivo antitumor efficacy across a series of myeloid malignancies. The product has previously received orphan drug designation and fast track designation from the U.S. FDA for the treatment ofEssential Thrombocythemia (ET)AndMyelofibrosis (MF)MSD has currently launched the pivotal Phase 3 randomized clinical trial MK-3543-006 to evaluate the efficacy of this product in treating patients with primary ET.

Previously, MSD announced the latest data from the Phase 2b MK-3543-003 trial at the 2023 American Society of Hematology (ASH) Annual Meeting. The study aims to evaluate bomedemstat alone or in combination with a JAK inhibitor.ruxolitinibTreatmentMyeloproliferative Neoplasms (MPN)Efficacy and safety. Myeloproliferative neoplasms are a type of blood cancer caused by the bone marrow producing too many red blood cells, platelets, or certain types of white blood cells, includingPrimary Thrombocythemia、Myelofibrosis、Polycythemia VeraThree types.

As of the data cutoff date on June 30, 2023, the study enrolled 16 males and 16 females with a median age of 64 years, and the median duration of ruxolitinib+bomedemstat was 12 weeks. Among the 20 evaluable patients at week 12,Hemoglobin (Hb) stabilization or improvement was achieved in 12 patients (60%), Total Symptom Score (TSS) reduction of ≥50% was observed in 5 patients (25%), and spleen length reduction of ≥30% was noted in 18 patients (65%).. In six patients, molecular response was assessed at week 12 by droplet digital polymerase chain reaction, and four patients (67%)JAK2 V617FAllele frequency decreased, with ≥50% reduction observed in 1 patient (17%).

Researchers believe that adding bomedemstat to the ruxolitinib regimen is well-tolerated, can improve splenomegaly and symptom scores, and stabilize hemoglobin levels.

References:
[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.Retrieved June 17，2024, From https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

[2]Global Phase 3 studies started for bomedemstat (LSD1 inhibitor), nemtabrutinib (BTK inhibitor), MK-2870 (anti-TROP2 ADC) and MK-5684 (CYP11A1 inhibitor). Retrieved Jan 5 , 2024, from https://www.merck.com/news/merck-announces-phase-3-trial-initiations-for-four-investigational-candidates-from-its-promising-hematology-and-oncology-pipeline/

[3]Phase 2 Study to Assess the Safety and Efficacy of Bomedemstat (MK3543) in Combination with Ruxolitinib in Patients with Myelofibrosis. Retrieved Nov , 2.2023, from https://ashpublications.org/blood/article/142/Supplement%201/621/499277/Phase-2-Study-to-Assess-the-Safety-and-Efficacy-of

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