Inrebic Approved to Treat Myelofibrosis
August 16, 2019 – The U.S. FDA has approved Inrebic® (fedratinib), manufactured by Celgene, to treat adult patients who have intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. It is the first new treatment for myelofibrosis to receive FDA approval in nearly a decade.
A rare form of bone cancer, myelofibrosis occurs at a rate of approximately 0.3 to 1.5 cases per 100,000 persons in European, Australian, and North American populations. Healthy bone marrow is replaced by fibrous (scar) tissue, which leads to a decrease in the production of blood cells. The disease is triggered by somatic mutations in the JAK2, MPL, CALR, and TET2 genes, but is not inherited. It can occur at any age, but is more commonly diagnosed in individuals over the age of 50. For the majority of patients, myelofibrosis will progress over time.
In a clinical study, 35 of 96 patients treated with the recommended dose of 400mg once daily experienced a 35% reduction of spleen volume (a measure of therapeutic effect). Thirty-six patients had a reduction of at least 50% in myelofibrosis-related symptoms, including night sweats, itching, abdominal discomfort, feeling full sooner than normal, pain under the ribs on the left side, and bone or muscle pain. The 400mg dose should only be used in patients who have a baseline platelet count of greater than or equal to 50 x 109/L, and modified for patients who have severe renal impairment or taking strong CYP3A inhibitors.
A black box warning cautions that there is a risk of serious and fatal encephalopathy with Inrebic, including Wernicke’s encephalopathy (a neurologic emergency). Prescribers should assess thiamine levels in all patients prior to starting Inrebic, periodically during treatment, and as clinically indicated. Patients with thiamine deficiency should not be started on Inrebic until thiamine levels have been restored. If encephalopathy is suspected, Inrebic should be discontinued immediately and the parenteral thiamine initiated. Patients should be monitored until resolution or improvement of symptoms resolve and normalization of thiamine levels.
Celgene has not yet announced launch or pricing information.