Fedratinib for the Treatment of Myelofibrosis: A Review of Clinical Trial and Real-World Data

Clinical Trial Data

• Phase I Trial (2011): Assessed fedratinib's safety, tolerability, and efficacy in patients with high- or intermediate-risk primary or post PV/ET MF. The maximum tolerated dose was 680 mg/day, with common adverse events including nausea, vomiting, diarrhea, anemia, and thrombocytopenia. Spleen volume response rates >35% (SVR35) were achieved by 39% of patients by week 24 and 47% at week 48.

• Phase II Study: Randomized 31 patients to receive fedratinib at 300, 400, or 500 mg once daily. The 400 mg dose showed the best spleen response, with 60% of patients responding at week 24, and also achieved the best symptom response.

• JAKARTA Study (Phase III): Involved 289 previously untreated patients with high-risk or intermediate-2 risk primary or post PV/ET MF. Patients were randomized to receive either 400 mg or 500 mg of fedratinib daily, or placebo. SVR35 was 36% for the 400 mg group and 40% for the 500 mg group at week 24, compared to 1% for placebo.

• JAKARTA-2 Study: Evaluated fedratinib in patients previously treated with ruxolitinib who demonstrated intolerance or disease progression. A SVR35 of 55% was achieved in evaluable patients, with a TSS response of 26%.

Real-World Data

• Mayo Clinic Experience: Reported on 28 MF patients relapsed or refractory to ruxolitinib. Spleen response was evaluated in 24 patients, with only three patients (13%) exhibiting a reduction in spleen size. Symptom improvement was more frequently reported.

• Community Oncology Practices Study: Included 150 patients previously treated with ruxolitinib. The mean spleen length decreased significantly from 16.0 cm at initiation to 7.2 cm at 6 months. Complete resolution of palpable spleen occurred in 21% of patients.

• Retrospective US Cohort Study: Described outcomes of 150 MF patients receiving fedratinib, pacritinib, or other therapies after ruxolitinib. The fedratinib arm showed a median overall survival (OS) of 27.1 months, with 96.6% of patients alive at 6 months post-index.

• Flatiron Health National Database Study: Compared survival in patients receiving fedratinib versus non-fedratinib therapy post-ruxolitinib. Median OS was not reached in the fedratinib group and was 17 months in the non-fedratinib group.

Conclusion

Fedratinib has shown efficacy in reducing spleen size and improving symptoms in patients with myelofibrosis, both in clinical trials and real-world settings. However, its benefits may be more pronounced in providing symptomatic relief rather than significant spleen size reduction. Adverse effects, particularly gastrointestinal and hematologic toxicities, are common but manageable.