FDA Approves JAK Inhibitor That Addresses Anemia in Myelofibrosis

The FDA approved momelotinib (Ojjaara) as the first therapy specifically for intermediate- and high-risk myelofibrosis with anemia, GSK announced.

Almost all patients with myelofibrosis develop anemia at some point during the course of the disease, and more than 30% ultimately discontinue treatment because of anemia. Momelotinib targets key manifestations of myelofibrosis, including anemia, constitutional symptoms, and splenomegaly.

"With momelotinib we have the potential to establish a new standard of care for myelofibrosis patients with anemia," said Ruben A. Mesa, MD, of Atrium Health Levine Cancer Center in Charlotte, North Carolina, in the company statement. "Addressing key manifestations of myelofibrosis ... makes a significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease."

Affecting an estimated 25,000 patients in the U.S., myelofibrosis arises from dysregulated Janus kinase (JAK) signaling. Distinct among JAK inhibitors, momelotinib has inhibitory activity along three signaling pathways involved in myelofibrosis pathogenesis: JAK1, JAK2, and activin A receptor type 1 (ACVR1). As described in the GSK announcement, inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly associated with myelofibrosis, and inhibition of ACVR1 leads to a decrease in circulating hepcidin, a contributing factor in anemia.

Principal support for the FDA approval came from the phase III MOMENTUM trial, which compared momelotinib with danazol in patients with persistent anemia and symptoms despite prior treatment with a JAK inhibitor. The trial met all primary and key secondary endpoints, demonstrating statistically significant improvement in symptoms, splenic response, and transfusion independence with momelotinib. Additional safety data came from a subgroup analysis of patients with anemia enrolled in the phase III SIMPLIFY-1 trial.

In both trials, the most common adverse events associated with momelotinib treatment were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.

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