Richard Pazdur, MD
On August 16, the U.S. Food and Drug Administration (FDA) approved the Janus kinase 2 (JAK2) inhibitor fedratinib (Inrebic) for the treatment of adults with intermediate-2 or high-risk primary or secondary (postpolycythemia vera or postessential thrombocythemia) myelofibrosis.
“Prior to [this approval], there was one FDA-approved drug to treat patients with myelofibrosis, a rare bone marrow disorder. Our approval provides another option for patients,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
Efficacy was investigated in JAKARTA, a double-blind, randomized, placebo-controlled trial in 289 patients with intermediate-2 or high-risk myelofibrosis, postpolycythemia vera myelofibrosis, or postessential thrombocythemia myelofibrosis with splenomegaly. Patients were randomly assigned to receive fedratinib at 500 mg (n = 97), fedratinib at 400 mg (n = 96), or placebo (n = 96) once daily for at least six cycles. The primary efficacy outcome was the proportion of patients achieving at least a 35% reduction from baseline in spleen volume at the end of cycle six measured by magnetic resonance imaging or computed tomography with a follow-up scan 4 weeks later.
Of the 96 patients treated with the recommended dose (400 mg) of fedratinib, 35 (37%) achieved at least a 35% reduction in spleen volume, compared with 1 of 96 patients who received placebo (P < .0001). The median duration of spleen response was 18.2 months for the 400-mg fedratinib group. In addition, 40% of patients who received 400 mg experienced at least a 50% reduction in myelofibrosis-related symptoms, whereas 9% of patients receiving placebo experienced a decline in these symptoms. ■