Celgene has secured approval from the US Food and Drug Administration (FDA) for its Inrebic (fedratinib) to treat adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis.
Inrebic is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). It is a JAK2-selective inhibitor with higher potency for JAK2 over family members JAK1, JAK3 and TYK2.
Inrebic reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation and induced apoptotic cell death in cell models expressing mutationally active JAK2 or FLT3.
Inrebic development programme is comprised of multiple studies, including Jakarta and Jakarta 2. The trials recruited 608 patients, receiving more than one dose ranging from 30mg to 800mg, of whom 459 had myelofibrosis and around 97% treated with ruxolitinib.
Myelofibrosis is a serious and rare bone marrow disorder, which disrupts the body’s normal production of blood cells.
The phase 3 multicentre, randomised, double-blind and placebo-controlled trial assessed the efficacy of once-daily oral doses of Inrebic compared with placebo in patients with intermediate-2 or high-risk primary or secondary myelofibrosis and a platelet count of ≥50 x 109/L who were previously untreated with a JAK inhibitor.
Celgene randomised 289 patients in the study to secure either Inrebic 500mg or placebo across 94 sites in 24 countries.
According to the company, the primary endpoint was spleen response rate, which is determined as the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at the end of cycle six as measured by magnetic resonance imaging (MRI) or computerized tomography (CT) with a follow-up scan four weeks later.
Celgene chief medical officer Dr Jay Backstrom said: “The approval of INREBIC is another important milestone for Celgene and underscores our commitment to people living with blood cancers.
“We are excited to provide INREBIC as a new treatment option that may be used in patients with myelofibrosis, including patients previously treated with ruxolitinib.”