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

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: 72% achieved durable platelet reduction (≤400 × 10⁹/L for ≥12 weeks)

• Primary Outcome: 77% (49/64) achieved response at 24 weeks (platelet count ≤400 × 10⁹/L without new thromboembolic events)

• Nnt Or Sensitivity: NNT approximately 1.3 for response (77% response rate)

• Confidence Interval: Not reported

Clinical Application

Requires specialized haematology centres with experience in myeloproliferative neoplasms and ability to monitor for adverse events Relevant for Australian haematology practice; would require TGA approval and PBS listing consideration given current limited options for refractory ET patients Adults with essential thrombocythemia who have failed or are intolerant to standard cytoreductive therapies (hydroxyurea, anagrelide, interferon)

Abstract

Novel treatments that can improve outcomes of essential thrombocythemia (ET) are needed. In a 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 × 109/L to 400 × 109/L). Primary end points were safety and response, defined as a platelet count of ≤400 × 109/L without new thromboembolic events. Of 73 who received bomedemstat, at 24 weeks, 49 of 64 evaluable participants (77%) achieved 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. This trial was registered at www.clinicaltrials.gov as #NCT04254978.

References

1. 1.Gill, H., Palandri, F., Ross, D. M., Göthert, J. R., Cochrane, T., Larsen, S. R., Halpern, A. B., Shortt, J., Rossetti, J. M., Liang, J., Marchetti, M., Wilson, A. J., Innes, A. J., Hanna, M., Vianelli, N., Stevenson, W. S., Vannucchi, A. M., Kleppe, M., Flynn, J., Natsoulis, G., Harrison, C. N., & Rienhoff, H. Y. (2026). Phase 2 study of the lysine-specific demethylase 1 inhibitor bomedemstat for essential thrombocythemia. Blood Advances. https://doi.org/10.1182/bloodadvances.2025017575