WILMINGTON, DE — Incyte (Nasdaq: INCY) reported updated early-stage clinical trial data showing its experimental antibody INCA033989 produced rapid and durable responses in patients with myelofibrosis and essential thrombocythemia, supporting plans to advance the treatment into late-stage studies for blood cancers driven by CALR mutations.
The data, presented at the European Hematology Association Congress in Stockholm, suggest the first-in-class antibody may not only control symptoms but also target the underlying disease biology in a subset of myeloproliferative neoplasms, an area where treatment options remain limited.
INCA033989 is designed to target mutant calreticulin (mutCALR), a genetic alteration found in certain patients with myelofibrosis (MF) and essential thrombocythemia (ET). The company said the therapy consistently reduced levels of the disease-driving mutation while generating clinical responses across both conditions.
In patients with myelofibrosis receiving INCA033989 as a standalone treatment, 39% achieved at least a 35% reduction in spleen volume, while 53% experienced at least a 50% reduction in symptom burden at some point during treatment.
Among evaluable patients with anemia, 60% achieved an anemia response and 52% experienced what investigators classified as a major anemia response.
The company reported that 89% of patients showed reductions in mutant CALR variant allele frequency, a molecular measure associated with disease activity. Researchers also observed reductions in disease-initiating stem and progenitor cells.
“Patients with CALR-mutated MF have distinct disease biology and often respond poorly to available therapies,” said Dr. Claire Harrison of Guy’s and St. Thomas’ NHS Foundation Trust. “What stands out in these data is that INCA033989 produced rapid and robust spleen, symptom and anemia responses, alongside reductions in mutCALR allele burden.”
The therapy was also evaluated in combination with Incyte’s JAK inhibitor partner therapy ruxolitinib among patients with suboptimal responses to existing treatment. At 24 weeks, 30% of patients achieved at least a 35% spleen volume reduction, while 31% achieved significant symptom improvement.
In essential thrombocythemia, the antibody generated stronger response rates.
Across all dose levels, 87% of patients achieved either a complete or partial hematologic response, while 70% achieved a complete hematologic response, defined by normalization of platelet and white blood cell counts.
The median time to a durable complete hematologic response was approximately two weeks, according to the data.
Investigators also reported a correlation between molecular responses and clinical outcomes. Among patients who achieved complete hematologic responses and had follow-up testing, 73% experienced at least a 25% reduction in mutant CALR levels.
“In patients with ET who were resistant to or intolerant of prior cytoreductive therapy, INCA033989 resulted in rapid and durable normalization of platelet counts with accompanying molecular responses,” said Dr. John Mascarenhas of the Icahn School of Medicine at Mount Sinai. “These results provide a strong foundation for advancing INCA033989 into a registrational Phase 3 study.”
The safety profile was generally favorable across both studies. No dose-limiting toxicities were reported in myelofibrosis, and no maximum tolerated dose was reached. Most patients remained on therapy at the time of data cutoff.
Among essential thrombocythemia patients, 95% remained on treatment, while severe adverse events were reported in 19% of participants. No severe thrombocytopenia events were observed.
Incyte said it plans to launch a Phase 3 trial in patients with CALR-mutated essential thrombocythemia by mid-2026. The U.S. Food and Drug Administration granted Breakthrough Therapy designation to INCA033989 in November 2025 for patients with Type 1 CALR-mutated essential thrombocythemia who are resistant or intolerant to prior cytoreductive therapy.
The company is also discussing a potential pivotal development program in myelofibrosis with regulators.
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