Introduction: Myeloproliferative neoplasms, such as essential thrombocythemia and myelofibrosis, cause vascular events and systemic symptoms sustained by platelet abnormalities and cytokine imbalance. Despite some recent advances, there is a need for novel therapies that can improve symptoms and alter the disease course. Bomedemstat is an irreversible inhibitor of lysine-specific demethylase 1, which is an epigenetic modifier involved in regulating megakaryocyte and erythrocyte maturation. Bomedemstat has shown manageable safety and promising clinical activity in myeloproliferative neoplasms, including essential thrombocythemia. However, long-term evaluation is needed. The nonrandomized, single-arm, active, open-label, phase 3 Shorespan-017 extension study (NCT06351631) was designed to assess the long-term safety, tolerability, and efficacy of bomedemstat in participants with myeloproliferative neoplasms who received prior treatment with bomedemstat in previous studies. Safety data for participants with essential thrombocythemia are reported.

Methods: Participants aged ≥18 years were transitioned from a bomedemstat study sponsored by Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, or MSD (feeder study). Participants from the IMG-7289-CTP-201/MK-3543-003 and IMG-7289-CTP-102/MK-3543-002 studies had to have received at least 6 months of treatment with bomedemstat, with manageable safety and clinical benefit per investigator assessment. All participants initiated bomedemstat at the same dose that was determined as safe and efficacious at the end of their feeder study. The primary end point was safety and tolerability. The data cutoff date was April 1, 2025.

Results: As of the data cutoff date, 56 participants were treated in the Shorespan-017 extension study, including 40 with essential thrombocythemia. For participants with essential thrombocythemia, the median study follow-up (time from treatment start date in this study to date of data cutoff) was 8.1 months (range, 3.5-10.3). The median age of participants was 68.5 years (range, 45-88); 23 (58%) were female, and 11 (28%) had an Eastern Cooperative Oncology Group performance status of 1. Of the 40 participants with essential thrombocythemia, 1 (3%) discontinued due to an adverse event of grade 4 anemia and 39 (98%) remained on treatment at data cutoff. All-cause adverse events of any grade occurred in 35 participants (88%), with the most common (incidence ≥10%) being diarrhea (23%), contusion (13%), abdominal pain (10%), and upper respiratory tract infection (10%). Grade 3 or 4 all-cause adverse events occurred in 8 (20%), and these events were anemia, anaphylactic reaction, atrial flutter, depressed mood, diarrhea, gastroenteritis, hyponatremia, inappropriate antidiuretic hormone secretion and tachycardia in 1 participant each (3%). No deaths due to all-cause adverse events occurred. Treatment-related adverse events of any grade occurred in 7 participants (18%); no grade 3-5 treatment-related adverse events were reported. One treatment-related serious adverse event was reported (3%, grade 2 constipation). Treatment-related adverse events were contusion and anemia in 2 participants each (5%); and arthralgia, constipation, cystitis, diarrhea, impaired gastric emptying, neutropenia, pain in extremity, and platelet count decreased in 1 participant each (3%). No discontinuations or deaths due to treatment-related adverse events occurred.

Conclusion: Bomedemstat had a manageable safety profile in participants with essential thrombocythemia who were currently receiving bomedemstat for longer duration in this extension study and achieved a clinical benefit.

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2025
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