WASHINGTON -- The the Janus kinase 2 (JAK2) inhibitor fedratinib (Inrebic) on Friday for adults with the rare bone marrow disease myelofibrosis.
Support for the approval came largely from the , a randomized three-arm trial that tested fedratinib at 400 mg or 500 mg versus placebo in 289 patients with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk primary myelofibrosis, or myelofibrosis following polycythemia vera or essential thrombocythemia.
In the 400 mg arm (the FDA's approved dose) 35 of 96 patients had at least a 35% reduction in spleen volume on MRI or CT scan at week 24. As the disease is characterized by scar tissue formation in the bone marrow, a symptom of the disease is spleen and liver enlargement as blood cell production moves from the bone marrow to these organs.
Additionally, 36 patients in the 400 mg arm had a 50% reduction in disease-related symptoms, which can include "night sweats, itching, abdominal discomfort, feeling full sooner than normal, pain under ribs on left side, and bone or muscle pain," according to the FDA.
The only other treatment for the disease -- the JAK1/2 inhibitor ruxolitinib (Jakafi) -- was approved in 2011.
"Prior to today, there was one FDA-approved drug to treat patients with myelofibrosis, a rare bone marrow disorder. Our approval today provides another option for patients," Richard Pazdur, MD, the top hematology/oncology official at the FDA, said in a statement. "The FDA is committed to encouraging the development of treatments for patients with rare diseases and providing alternative options, as not all patients respond in the same way."
Approval of fedratinib comes despite concerns over Wernicke's encephalopathy, a neurologic emergency linked to thiamine deficiency. Clinical development of the drug was halted in 2013 after eight of 670 patients treated with fedratinib in the phase II/III trials developed symptoms suggestive of Wernicke's. The label for the drug will include a boxed warning due to the risk of serious and fatal encephalopathy, including Wernicke's.
Non-clinical studies, however, the drug's ability to inhibit thiamine uptake and link to the serious neurological disorder.
In the phase III JAKARTA study of fedratinib, the most common adverse event (AE) was diarrhea (66%), and prophylactic medications may be recommended. Other AEs noted in the FDA's approval include nausea, vomiting, fatigue, and muscle spasms. Healthcare professionals are also advised to look for severe anemia and thrombocytopenia and monitor patients for gastrointestinal and hepatic toxicities.