Fedratinib is “Uniquely Positioned” in MDS/MPN Treatment

Data from a phase 2 study (NCT05177211) presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO) showed that fedratinib (Inrebic) produced promising clinical efficacy in patients with myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) and those with chronic neutrophilic leukemia (CNL) harboring proliferative features. These findings indicated that fedratinib’s unique inhibition profile may facilitate enhanced efficacy in these patient populations over other standard strategies.

In a conversation with CancerNetwork^®, presenting study investigator Andrew Kuykendall, MD, elaborated on these trial findings and explained why fedratinib is uniquely positioned as a therapeutic strategy for these patients. Compared with other standards of care, fedratinib can target MYC, JAK2 mutations, and other proliferative pathways in MDS/MPN overlap syndromes.

Kuykendall is an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center.

Transcript:

Fedratinib is a JAK inhibitor, but it certainly works on the broader JAK-STAT pathway. We know that in patients with myelofibrosis and myeloproliferative neoplasms, you certainly upregulate that JAK-STAT pathway, and many patients with MDS/MPN overlaps actually upregulate that JAK-STAT pathway. About a third of our patients had JAK2 mutations. We also saw some mutations in CSF3R, which actually goes through that JAK-STAT pathway as well.

The challenge is that there are other proliferative pathways that our standard JAK inhibitors don’t necessarily hit that well. We think about RAS pathway mutations and things that are driven through MYC, and that’s what is particularly interesting in MDS/MPN overlap syndromes; a lot of them upregulate this MYC pathway. Fedratinib is actually a potent MYC suppressor, so this is the reason why we think that fedratinib is actually uniquely positioned for this group of diseases: it hits JAK2, so it addresses that upregulated pathway, but it also hits some other proliferative pathways that might be less addressable with our current standard of care.

Reference

Kuykendall AT, Jain T, Singh A, et al. A phase 2 study of fedratinib in patients with MDS/MPN and chronic neutrophilic leukemia. J Clin Oncol. 2026;44(suppl 16):6509. doi:10.1200/JCO.2026.44.16_suppl.6509