bomedemstat (MK-3543)

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]).

P1, N=9, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | N=24 --> 9

P2, N=40, Not yet recruiting, United Lincolnshire Hospitals NHS Trust

Several PROTAC therapies are now in AML trials. LSD1-targeted degradation is promising, but further research is needed to confirm its safety, overcome resistance, and identify optimal drug combinations for AML treatment.

P1, N=24, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Glioblastoma stem cell (GSC) lines and normal human astrocytes (NHAs) were treated with catalytic LSD1 inhibitors, NCD38 and bomedemstat, and the LSD1 scaffolding inhibitor, seclidemstat alone and in combination with kinase inhibitors, including osimertinib, afatinib, and ulixertinib. Combined treatment with NCD38 and osimertinib in glioblastoma-bearing mice delayed tumor growth and improved survival outcomes. These findings provide a rationale for further investigation of combination therapies of catalytic inhibitors of LSD1 and EGFR and dual-targeted inhibitors to overcome resistance and improve outcomes.

P1, N=24, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Nov 2025 --> Mar 2026

P3, N=340, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Sep 2026 --> Jul 2027

P3, N=300, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Apr 2029 --> Mar 2028

Key trials include the phase 2 LSD1 inhibitor bomedemstat trial showing significant platelet-count reduction and mutation-burden improvement the phase 3 SURPASS-ET trial comparing ropeginterferon alfa-2b versus anagrelide, ongoing investigations of JAK - STAT pathway modulators, and emerging data on the anti-calreticulin (CALR) monoclonal antibody INCA033989, which selectively targets mutCALR progenitors to suppress malignant hematopoiesis while sparing normal hematopoiesis. Drawing on recent clinical trials, expert consensus, and emerging data presented at hematology meetings (2018-2025), we highlight established cytoreductive strategies - hydroxyurea, interferon-α (including pegylated formulations), and anagrelide - and evaluate emerging targeted agents. Future advances in ET management hinge on integrating molecular risk stratification into treatment algorithms, optimizing combination regimens to deepen molecular remissions, and prioritizing agents with favorable safety profiles. Personalized approaches leveraging allele-burden dynamics and symptom-control metrics are likely to define the next era of ET pharmacotherapy.

P3, N=300, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Apr 2027 --> Sep 2027

P2, N=9, Active, not recruiting, The University of Texas Health Science Center at San Antonio | Completed --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2026