▎Edited by the WuXi AppTec content team

According to the latest announcement on the Chinese Drug Clinical Trial Registration and Information Disclosure Platform, Merck & Co., Inc. (MSD)Used for treatmentPrimary ThrombocythemiaClass 1 Oral New DrugMK-3543（Bomedemstat) initiates Phase 3 clinical trial.BomedemstatIs aOral lysine-specific demethylase 1 (LSD1) inhibitor,MSD spent approximately US$1.35 billion in 2022AcquisitionImago BioSciences, thereby acquiring this drug candidate.

The public information shows that thisIs an international multicenterPhase 3, Randomized, Open-label, Active-controlled Clinical StudyIn subjects with primary thrombocythemia who have poor response to or are intolerant of hydroxyureaEvaluationSafety and Efficacy of Bomedemstat Compared to Best Available Therapy (BAT)According to the trial protocol, the investigational drug is a capsule formulation for daily oral administration, with an initial dose of 50mg QD (once daily). The dose will be adjusted based on hematological assessments, and the treatment can last up to 156 weeks.The target number of participants for patient recruitment isChina40 people in China, 300 people internationally.

Screenshot Source：China Drug Clinical Trial Registration and Information Disclosure Platform Official Website

Histone Lysine-Specific Demethylase 1 (LSD1)It is an epigenetic regulatory protein.It is generally overexpressed in many types of cancer, leading to blocked cell differentiation.Increased proliferation, migration, and invasiveness.Pharmacological studies have shown that someLSD1 TargetingSmall molecule inhibitors exhibit inhibitory effects on cancer cell differentiation, proliferation, invasion, and migration.Due to the significant role of LSD1 in carcinogenesis and its various mechanisms of interfering with signaling pathways, targeting LSD1 is considered a promising approach for cancer treatment.

Bomedemstat isOne of the products with rapid research and development progress in the field of LSD1-targeted inhibitors. This product was initially developed byImago BioSciencesR&D,MSD spent approximately US$1.35 billion in 2022AcquisitionCompletedImago, thereby acquiring this drug candidate.In non-clinical studies,bomedemstatDemonstrates potent antitumor efficacy across a series of myeloid malignancies. Moreover,The product has been previouslyGranted by the U.S. FDAOrphan Drug Designation and Fast Track Designation, respectivelyUsed for treatmentEssential Thrombocythemia (ET)AndMyelofibrosis (MF)。

According to the Phase 2b study data presented by Merck & Co., Inc. (MSD) at the 2023 American Society of Hematology (ASH) Annual Meeting, bomedemstat alone or in combination with a JAK inhibitor...ruxolitinibTreatmentMyeloproliferative Neoplasms (MPN)Efficacy and Safety ResultsPositive.The researchers pointed out that the combination regimenWell tolerated, can improve splenomegaly and symptom scores, and stabilize hemoglobin.。Myeloproliferative neoplasms are a class ofLeukemia, includingPrimary Thrombocythemia、Myelofibrosis、Polycythemia VeraThree Types。

Public information shows that MSD is currently conductingbomedemstatA pivotal Phase 3 randomized clinical trial to evaluate its efficacy in treating patients with Essential Thrombocythemia (ET). The initiation of this Phase 3 study in China signifies that the drug's efficacy and safety will also be investigated in the Chinese patient population.

Public data shows that currently, several LSD1 inhibitors have entered clinical trials for cancer treatment globally. Among them, multiple ones can be used withFAD CofactorThe product pipeline of covalent binding has entered the clinical development stage, such asiadademstat、bomedemstat、GSK-2879552、INCB059872、JBI-802Etc. SomeNon-covalent LSD1 inhibitors have also been studied and reported, such as pulrodemstat andseclidemstatetc. have allEntering clinical development. In addition, a dual LSD1/MAO-B targeted inhibitor, vafidemstat, is currently undergoing clinical trials for Alzheimer's disease and personality disorders.

[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

[4]LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials.Retrieved Feb 2，2023, From  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932783/