Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat for essential thrombocythemia

Novel treatments that can improve disease course of essential thrombocythemia (ET) are needed. In this phase 2 trial, participants with ET who required cytoreduction and had inadequate response to or were intolerant of ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200-400×109/L). Primary end points were safety and response, defined as a platelet count ≤400×109/L without new thromboembolic events. Seventy-three participants received bomedemstat. At 24 weeks, 49 of 64 evaluable participants (77%) had a response. Durable reductions in platelet count (≤400×109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10×109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10×109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. Registration: NCT04254978 (Study of Bomedemstat in Participants With Essential Thrombocythemia [IMG-7289-CTP-201/MK-3543-003]).

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Publication Details

Journal
Blood Advances
Published
2026-02-27
DOI
https://doi.org/10.1182/bloodadvances.2025017575
Primary Topic
Myeloproliferative Neoplasms: Diagnosis and Treatment
Type
article
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article

Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat for essential thrombocythemia

James M. Rossetti, Stephen Robert Larsen, Andrew J. Innes, Hugh Young Rienhoff et al.
Blood Advances
Myeloproliferative Neoplasms: Diagnosis and Treatment
article

Phase 2 study of the lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat for essential thrombocythemia

James M. Rossetti, Stephen Robert Larsen, Andrew J. Innes, Hugh Young Rienhoff, Georges Natsoulis, William Stevenson, Tara Cochrane, David M. Ross, Andrew J. Wilson, James Liang, Jessica A. Flynn, Anna B. Halpern, Monia Marchetti, Jake Shortt, Merit Hanna, Nicola Vianelli, Alessandro M. Vannucchi, Harinder Gill, Joachim R Göthert, Francesca Palandri, Claire N. Harrison
article en

Abstract

Novel treatments that can improve disease course of essential thrombocythemia (ET) are needed. In this phase 2 trial, participants with ET who required cytoreduction and had inadequate response to or were intolerant of ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200-400×109/L). Primary end points were safety and response, defined as a platelet count ≤400×109/L without new thromboembolic events. Seventy-three participants received bomedemstat. At 24 weeks, 49 of 64 evaluable participants (77%) had a response. Durable reductions in platelet count (≤400×109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10×109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10×109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. Registration: NCT04254978 (Study of Bomedemstat in Participants With Essential Thrombocythemia [IMG-7289-CTP-201/MK-3543-003]).

Blood Advances
Merck & Co., Inc., Rahway, NJ, USA (United States) (US), Royal Adelaide Hospital (AU), University College London Hospitals NHS Foundation Trust (GB), Imperial College Healthcare NHS Trust (GB), Chinese University of Hong Kong (HK), Guy's and St Thomas' NHS Foundation Trust (GB), Royal Prince Alfred Hospital (AU), Royal North Shore Hospital (AU), Gold Coast Hospital (AU), Middlemore Hospital (NZ), North Shore Hospital (NZ), Fred Hutch Cancer Center (US), Waitemata District Health Board (NZ), Azienda Ospedaliero-Universitaria Careggi (IT), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), Monash Health (AU), UPMC Hillman Cancer Center (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), Ovid Therapeutics (United States) (US), University College London (GB), University of Hong Kong (HK)
Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Leukemia and Lymphoma Society, Gilead Sciences, Celgene, AbbVie, Karyopharm Therapeutics, Jazz Pharmaceuticals, Astex Pharmaceuticals, BeiGene, Incyte, Galecto, British Society for Haematology, Novo Nordisk, Astellas Pharma, Swedish Orphan Biovitrum, Grifols, Division of Materials Research, Cilag
Good health and well-being
Openalex Percentile: Top 42%
Myeloproliferative Neoplasms: Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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