Fedratinib

Current understanding

Selective JAK2 inhibitor approved for intermediate-2 and high-risk myelofibrosis (JAKARTA). Active in ruxolitinib-failure setting.

Evidence log

• 2026-09-24 — Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling.: Preclinical study reports synergistic activity when fedratinib is combined with the TYK2 inhibitor deucravacitinib against CALR- and MPL-mutant MPN cells, suggesting a mutation-selective combination rationale distinct from JAK2V617F disease. (novelty: 5)
• 2026-08-13 — Study of Flonoltinib Maleate Tablets in the Treatment of Proliferative Bone Marrow Tumors: Comparator context (preclinical → trial-early): flonoltinib maleate reported preclinical superiority in JAK2 selectivity and toxicity profile versus fedratinib, entering early clinical testing across MF, PV, and ET. (novelty: 3)
• 2026-09-01 — Matching-Adjusted Indirect Comparison of Gecacitinib, Fedratinib, Pacritinib, and Momelotinib in Second-Line Myelofibrosis Therapy.: MAIC (observational, indirect comparison) in ruxolitinib-pretreated MF ranked fedratinib below gecacitinib on spleen-volume and symptom responses and flagged higher GI adverse-event and discontinuation rates relative to gecacitinib. (novelty: 3)
• 2026-08-14 — Janus kinase inhibitors after ruxolitinib failure in myelofibrosis: A systematic review and pooled analysis of phase 3 efficacy and integrated safety across clinical trials and real-world evidence.: Systematic review + pooled phase-3/real-world meta-analysis positions fedratinib in the post-ruxolitinib salvage landscape with a distinct spleen/symptom/safety fingerprint (notable GI toxicity and Wernicke-encephalopathy monitoring signal) versus momelotinib and pacritinib, informing phenotype-driven second-line JAKi selection. (novelty: 3)
• 2026-04-17 — Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL): Prospective phase 2 trial (trial-early) evaluating fedratinib efficacy, safety, and tolerability in MDS/MPN overlap syndromes (MDS/MPN-U, MDS/MPN-RS-T, aCML) and chronic neutrophilic leukemia — first formal evaluation of this JAK2 inhibitor in these rare subtypes. (novelty: 3)
• 2026-04-08 — Fedratinib in Combination With Nivolumab: Phase II trial (trial-early) pairs fedratinib with the PD-1 inhibitor nivolumab in JAK-inhibitor-resistant/suboptimal-response myelofibrosis — a novel immune-checkpoint combination strategy extending fedratinib’s role beyond monotherapy in second-line MF. (novelty: 4)
• 2026-04-08 — A Clinical Trial of Flonoltinib Maleate Tablets in the Treatment of JAK Inhibitor Refractory/Relapsed/Intolerant Patients With Medium to High Risk Myelofibrosis: cross-connection with flonoltinib-maleate-mpn: Both target the post-ruxolitinib refractory/intolerant MF niche; comparator framing for second-line JAK inhibition. (novelty: 4)
• 2026-03-16 — Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms: Phase II trial (trial-early): fedratinib being evaluated as one of three JAK inhibitor options combined with decitabine as pre-transplant bridging therapy in accelerated/blast phase MPN — first evaluation of fedratinib in AP/BP-MPN bridging context. (novelty: 3)
• April 28, — Fedratinib Shows Promise in MDS/MPN Overlap Syndromes and CNL: Phase 2 trial (early data) showed promising efficacy and manageable safety in MDS/MPN overlap syndromes (MDS/MPN-U, MDS/MPN-RS-T, aCML) and chronic neutrophilic leukemia, expanding potential indications beyond myelofibrosis. (novelty: 4)

Open questions

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