Key Takeaways:
Incyte's INCA033989 achieved a 70% complete response rate in essential thrombocythemia and 27% spleen reduction in myelofibrosis at week 24, per EHA 2026 data.
"The data demonstrate clinically meaningful and consistent responses with INCA033989 across both myelofibrosis and essential thrombocythemia," Pablo J. Cagnoni, president and global head of R&D at Incyte, said.
In the ET study, 70% of 114 patients achieved complete hematologic response, with a median time to response of 2.1 weeks. Among Type 1 CALR mutation patients, 81% achieved durable CHR at doses of 750 milligrams and above, while 50% of non-Type 1 patients achieved durable CHR or partial hematologic response at 2,500 milligrams. In MF, the drug delivered a 27% spleen volume reduction rate at week 24 as monotherapy in patients who had failed prior JAK inhibitor treatment, and 30% when combined with ruxolitinib. Anemia response occurred in 60% of evaluable MF patients, with 52% achieving a major anemia response.
The results position INCA033989 as a potential first-in-class therapy targeting CALR mutations, which drive 25% to 35% of ET and MF cases. Incyte received FDA Breakthrough Therapy designation for the drug in ET in November 2025 and is initiating a Phase 3 study, EXCALIBUR-ET2, in mid-2026.
The drug also showed molecular activity across both indications. In MF, 89% of patients achieved a reduction in mutant CALR allele burden in whole blood, and 81% saw at least a 25% reduction in peripheral blood mononuclear cells. In ET, 73% of patients who achieved CHR saw at least a 25% reduction in variant allele frequency. Clinical responses occurred regardless of mutational complexity, with 93% of MF patients with high molecular risk mutations showing VAF reduction.
Safety data showed 84% of MF patients and 95% of ET patients remained on treatment, with no dose-limiting toxicities observed. In MF, Grade 3 or above treatment-emergent adverse events occurred in 27% of patients, most commonly cytopenias, with only two discontinuations due to adverse events. In ET, Grade 3 or above events occurred in 19% of patients, with no Grade 3 or above thrombocytopenia reported.
The data come as Eli Lilly's Ajax Therapeutics unit presents competing Phase 1 data at the same conference for its Type II JAK2 inhibitor AJ1-11095, which showed a 70% best SVR35 rate in 23 pretreated MF patients. While Lilly's candidate targets a broader patient population through JAK2 inhibition, Incyte's approach is mutation-specific, targeting only CALR-driven disease.
The broad efficacy across two indications and the molecular response data support INCA033989's potential as a disease-modifying therapy. Investors will watch for enrollment updates on the Phase 3 ET study and regulatory discussions for a pivotal MF program.
This article is for informational purposes only and does not constitute investment advice.
