Incyte’s Antibody Shows Promise for Treating Rare Blood Cancer

Incyte Corporation has announced promising early-stage clinical results for an experimental precision antibody, INCA033989, which has demonstrated significant efficacy in patients with essential thrombocythemia. The findings, presented at the American Society of Hematology’s annual meeting in March 2025, reveal that nearly 90 percent of patients receiving higher doses achieved a hematologic response, with over 83 percent reaching a complete response characterized by normalized platelet and white blood cell counts.

INCA033989 is a first-in-class monoclonal antibody specifically designed to target mutant calreticulin, a genetic mutation found in approximately 25 to 33 percent of essential thrombocythemia cases. This condition is often associated with aggressive disease progression and limited treatment options, as existing therapies generally suppress blood cell production rather than addressing the underlying mutation directly.

Significant Improvements in Disease Markers

Beyond improvements in blood counts, Incyte’s latest data indicate rapid and durable molecular responses among patients. Follow-up measurements revealed that nearly all participants showed reductions in mutant CALR variant allele frequency, a critical marker of disease burden. Approximately 50 percent of patients recorded reductions of at least 25 percent, while nearly one-third achieved reductions of 50 percent or more. Higher doses were associated with deeper and more consistent responses, suggesting that INCA033989 may have the potential to modify disease biology rather than merely alleviate symptoms.

Exploratory analyses provided additional insights, indicating that the drug may directly reduce mutant stem and progenitor cells and improve abnormal bone marrow cell growth. These findings suggest potential disease-modifying activity, which could represent a significant advancement in treatment options for this patient population.

Promising Safety Profile and Regulatory Support

The safety profile of INCA033989 is also encouraging, with no dose-limiting toxicities reported and a maximum tolerated dose not yet reached. Most adverse events were classified as mild to moderate, with common issues including fatigue, headache, upper respiratory infections, and anemia. Notably, only one patient discontinued treatment due to side effects, underscoring the manageable nature of the drug’s adverse effects.

In recognition of its potential, the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to INCA033989 for patients with Type 1 CALR-mutated essential thrombocythemia who are resistant or intolerant to previous cytoreductive therapies. This designation is expected to expedite the drug’s development and review process.

Incyte plans to advance INCA033989 into a registrational program covering both Type 1 and non-Type 1 CALR mutations. This strategic move positions the drug as a potential leader in mutation-specific treatment for myeloproliferative neoplasms, a group of disorders characterized by the overproduction of blood cells.

For investors, these developments enhance Incyte’s pipeline narrative, highlighting a novel, targeted approach with early signs of durable efficacy and a manageable risk profile. This combination is increasingly valued in the fields of oncology and rare disease drug development, as the industry seeks effective treatments for conditions with limited options.