Incyte Corporation (INCY) unveiled some encouraging clinical data over the weekend that suggests its experimental therapy might actually modify the course of a rare blood cancer, not just manage symptoms.
The company presented Phase 1 results for INCA033989 at the 2025 American Society of Hematology Annual Meeting, focusing on patients with myeloproliferative neoplasms carrying specific CALR gene mutations. Think of these as blood cancers where the bone marrow goes into overdrive producing blood cells.
The preliminary data, with a cutoff date of September 25, 2025, looked at how well the drug worked in myelofibrosis patients across several measures: spleen shrinkage, symptom relief, anemia improvement, and reduction in the mutated gene variants driving the disease.
How Patients Responded When Taking INCA033989 Alone
The monotherapy results show the drug delivers on multiple fronts. By week 24, about 42% of evaluable patients saw their spleen volume drop by at least 25%, while one-third achieved a 35% reduction or more. Those numbers get more impressive when you look at treatment-naive patients who hadn't previously tried JAK inhibitors.
Among patients new to JAK inhibitor therapy, 71.4% hit that 25% spleen reduction threshold, and 57.1% reached the more stringent 35% mark. Even in the tougher crowd—patients who'd already failed or couldn't tolerate JAK inhibitors—about a third still responded with meaningful spleen reduction.
The anemia data looks particularly promising. More than half of anemic patients showed improvement, with 40% achieving what researchers call a major response. That matters because anemia is one of the more debilitating aspects of myelofibrosis.
Nearly everyone on the drug (93.3%) reported better symptoms, and 60% saw their total symptom score drop by at least half at some point during treatment. At the 24-week mark specifically, 39.4% maintained that 50% symptom improvement.
Here's where it gets interesting from a disease-modification perspective: Most patients with follow-up genetic testing (89.4%) showed a reduction in their mutated CALR variant allele frequency. That's science-speak for saying the proportion of cancer cells carrying the problematic mutation decreased. About 11% of patients saw their mutated gene frequency drop by at least 25%.
The drug also appeared to work even in complicated cases. Three-quarters of study participants had additional mutations beyond CALR, yet among response-eligible patients in this group, 40.5% still achieved either significant spleen reduction or anemia improvement. Single-cell genetic analyses showed the therapy consistently reduced all CALR-mutant cell populations, regardless of what other mutations were hanging around.
Combination Therapy Results
When researchers paired INCA033989 with ruxolitinib, a standard JAK inhibitor, most patients experienced spleen shrinkage and symptom relief. At week 24, half of evaluable patients hit the 25% spleen reduction target, and a quarter reached 35% reduction.
Among 14 evaluable patients, 86% maintained stable anemia levels, and one patient without transfusion-dependent anemia achieved a major anemia response. The majority (81.3%) reported improved symptoms, with one-third achieving that 50% symptom score reduction at week 24.
The safety profile looked manageable whether patients took INCA033989 alone or combined with ruxolitinib, according to the company.
What Comes Next
Beyond myelofibrosis, Incyte is testing INCA033989 in Phase 1 studies for essential thrombocythemia, another blood disorder driven by CALR mutations. The company plans to launch a registrational program in 2026 targeting ET patients with CALR mutations who've failed or can't tolerate existing cytoreductive therapies.
INCY Price Action: Incyte shares traded down 2.46% at $99.99 during premarket activity on Monday.
