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FDA approves Inrebic for myelofibrosis
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The FDA today approved fedratinib for the treatment of adults with intermediate-2 or high-risk primary or secondary myelofibrosis.
“Myelofibrosis can cause patients to suffer in many ways, including experiencing debilitating symptoms,” Ruben Mesa, MD, FACP, director of the Mays Cancer Center at UT Health San Antonio Cancer Center MD Anderson and a HemOnc Today Editorial Board Member, said in a company-issued press release. “There has not been a new treatment approved for this disease in nearly a decade. With Inrebic, physicians and patients now have another option available for myelofibrosis.”
The approval of fedratinib (Inrebic; Impact Biomedicines, Celgene) — a highly selective JAK2 inhibitor — is based on data from the double-blind, randomized, placebo-controlled JAKARTA trial, which included 289 patients with intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with splenomegaly. All patients had not previously received a JAK inhibitor, had splenomegaly and had a platelet count of 50 x 109/L or higher.
Researchers randomly assigned patients to receive 500 mg fedratinib (n = 97), 400 mg fedratinib (n = 96) or placebo (n = 96) daily for at least six cycles.
The proportion of patients achieving at least a 35% reduction from baseline in spleen volume by the end of cycle 6 — measured by MRI or CT with a follow-up scan 4 weeks later — served as the study’s primary endpoint.
Thirty-five patients (37%) who received the recommended 400-mg dose of fedratinib achieved the primary endpoint, compared with one patient who received placebo (P < .0001). Median duration of spleen response in the 400-mg dose group was 18.2 months.
Forty percent of patients who received 400-mg fedratinib experienced at least a 50% reduction in myelofibrosis-related symptoms — which include night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, bone or muscle pain, as measured by the Total Symptom Score of the modified Myelofibrosis Symptoms Assessment Form v2.0 diary —compared with only 9% of patients assigned placebo (P < .001).
The most common adverse reactions associated with fedratinib included diarrhea, nausea, anemia and vomiting. Twenty-one percent of patients receiving 400-mg fedratinib experienced serious adverse events, the most common of which were cardiac failure (5%) and anemia (2%).
Fedratinib includes a boxed warning about serious and fatal encephalopathy — including Wernicke encephalopathy, a neurologic emergency resulting from thiamine deficiency — which occurred in 1.3% of patients (n = 8 of 608) treated with the agent across clinical trials. One of these cases (0.16%) was fatal.
Fedratinib previously received priority review and orphan drug designation.
“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, 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, said in a press release. “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.”