ASH 2025: Myelofibrosis Roundup
Key claim: INCA033989, a first-in-class antibody targeting mutant calreticulin, demonstrated high treatment retention (87%), spleen volume reduction, anemia improvement, and symptom reduction in Phase 1 myelofibrosis patients, including those resistant or intolerant to JAK inhibitors.
Abstract
Coverage of ASH 2025 meeting presentations including preliminary Phase 1 data on INCA033989, a first-in-class antibody targeting mutant calreticulin (CALR) with activity in myelofibrosis patients. The antibody showed 87% of patients still on treatment at data cutoff, with spleen volume reduction, anemia improvement, and symptom reduction. Notably effective in JAK inhibitor-resistant/intolerant patients.
Why this matters
INCA033989 is the first therapy to directly target the mutant calreticulin neoepitope, opening a disease-modifying mechanism distinct from JAK inhibition that nonetheless produced concurrent spleen, anemia, and symptom improvements in early myelofibrosis data. For symptom management this matters because it suggests upstream immunologic clonal targeting may resolve multiple symptom drivers simultaneously — including in JAK-inhibitor-resistant or intolerant patients who currently have few symptom-control options.