FDA Approves Fedratinib for Patients With Myelofibrosis

The Food and Drug Administration (FDA) approved fedratinib (Inrebic) for the treatment of patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis.

The approval was based off the JAKARTA and JAKARTA2 studies, which involved 608 patients who had 1 or more dose of the drug. In the study population, 459 patients had myelofibrosis, and 97 of them were previously treated with ruxolitinib (Jakafi).

According to Michelle Woehrle, executive director, MPN Research Foundation, nurses are crucial in treating these patients.

"Nurses play a critical role. They are the front line in ensuring patients are aware of the breadth of options, and of support that they can access. Not just financial support for copays or drug reimbursement but for the emotional support, disease education and community that is offered by groups like MPN Research Foundation and others. We try to ensure nurses and doctors who see people living with myeloproliferative neoplasms have access to the materials we produce as well as information about our patient registry myMPN, all of which are completely free."

JAKARTA compared the safety and efficacy of fedratinib compared to placebo in patients with intermediate-2 or high-risk primary or secondary myelofibrosis who had once daily doses of the drug. Patients were previously untreated with a JAK inhibitor, had splenomegaly, and had a platelet count of ≥50 x 10⁹/L.

“The approval of Inrebic is another important milestone for Celgene and underscores our commitment to people living with blood cancers,” said Jay Backstrom, MD, MPH, Chief Medical Officer for Celgene, the manufacturer of the drug. “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.”

Results from JAKARTA showed that spleen volume was reduced by 35% or more between baseline and the end of 6 cycles, which lasted 24 weeks, with a 4-week follow-up, 35 of 96 patients given 400 mg of fedratinib compared to 1 of 96 of patients given a placebo. Patients on the fedratinib arm also improved the Total Symptom Scores measured by the Myelofibrosis Symptoms Assessment form by 50% or more in 40% of patients on the drug. The symptom score measures maladies such as night sweats, itching, abdominal discomfort, early satiety, pain under ribs on the left side, bone pain, and muscle pain.

“Myelofibrosis can cause patients to suffer in many ways, including experiencing debilitating symptoms,” said Ruben Mesa, MD, FACP, Director of the Mays Cancer Center at UT Health San Antonio Cancer Center MD Anderson, in a statement. “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.”

Twenty-one percent of patients treated with fedratinib experienced serious adverse events (AEs) in the JAKARTA study. The most common (occurring in 2% or more of patients) included: cardiac failure and anemia. One percent of patients had a fatal adverse reaction of cardiogenic shock.

Additionally, 14% of patients had had to permanently stop taking the drug due to an AE. The most common reasons for this were: cardiac failure, thrombocytopenia, myocardial ischema, diarrhea, and increased blood creatinine.

Dose interruptions occurred in 21% of patients taking fedratinib on the JAKARTA trial. Common reasons (occurring in 3% or more of patients) were diarrhea and nausea. Nineteen percent of patients ended up having the drug dose reduced, with common reasons being anemia, diarrhea, vomiting, and thrombocytopenia.

Fedratinib has a Boxed Warning for serious and fatal encephalopathy, including Wernicke’s, which is a neurologic condition caused by a thiamine (Vitamin B1) deficiency. This was reported in 1.3% of patients on a clinical trial for the drug; 0.16% of the cases were fatal. Nurses and other healthcare providers should assess thiamine levels before starting their patients on fedratinib, and monitor these levels periodically during treatment as well.

This approval marks the first new treatment for this patient population in nearly a decade.

“Inrebic is a much-welcomed new treatment for the myelofibrosis community,” said Ann Brazeau, Chief Executive Officer and Founder, MPN Advocacy and Education International, in a statement. “This FDA approval marks an important milestone for people living with myelofibrosis as we embark on making greater strides in the diagnosis, understanding and treatment of this disease.”