FDA Grants Priority Review to Investigational Treatment for Myelofibrosis

Officials with the FDA have granted Priority Review to Celgene’s fedratinib, a highly selective Janus associated kinase 2 (JAK2) inhibitor for the treatment of myelofibrosis, according to a press release.

Myelofibrosis, a rare bone marrow disorder, disrupts the body’s normal production of blood cells and gradually replaces bone marrow with fibrous scar tissue. Patients with the disease can experience anemia, weakness, fatigue, and swelling of the spleen and liver, among other symptoms, according to Celgene.

Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated JAK2 and FMS-like tyrosine kinase 3. In mouse models, fedratinib blocked phosphorylation of signal transducer and activator of transcription proteins, increased survival, and improved disease-associated symptoms, including reduction of white blood cells, hematocrit, splenomegaly, and fibrosis.

There is currently only 1 FDA-approved treatment for myelofibrosis, ruxolitinib, which was approved in 2011.

The FDA’s acceptance of the New Drug Application (NDA) for fedratinib is based on data from the phase 2 JAKARTA2 trial and phase 3 JAKARTA trial. In the JAKARTA trial, treatment with daily oral doses of 400 mg or 500 mg of fedratinib were compared with placebo in patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with splenomegaly.

The JAKARTA2 trial evaluated the efficacy of a once-daily dose of fedratinib at a 400 mg starting dose in patients previously treated with ruxolitinib and with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis.

Fedratinib has also received Orphan Drug designation from the FDA for the treatment of secondary and primary myelofibrosis.

“The acceptance of the NDA and granting of Priority Review for fedratinib represent the first potential new treatment option after many years for patients affected by myelofibrosis,” said Jay Backstrom, MD, chief medical officer for Celgene. “Patients with myelofibrosis, including the number who are ineligible for or failed existing therapy continues to increase, representing a well-defined unmet medical need. We believe fedratinib can play an important role in the treatment of myelofibrosis and we look forward to working with the FDA as the review process advances.”

Additionally, Celgene also plans to evaluate fedratinib in combination with luspatercept, an experimental drug being developed for the treatment of anemia in beta thalassemia and myelodysplastic syndrome.

Under the Prescription Drug User Fee Act, the FDA’s estimated action date is September 3, 2019, according to the press release.

Reference

US FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis [news release]. Celgene. https://ir.celgene.com/press-releases/press-release-details/2019/US-FDA-Grants-Priority-Review-for-Fedratinib-New-Drug-Application-in-Myelofibrosis/default.aspx. Accessed March 5, 2019.