Updated Analysis Supports Evaluation of Second-Line Fedratinib to Treat Myelofibrosis

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Treatment with fedratinib may lead to clinically meaningful responses among patients with myelofibrosis who were previously treated with Jakafi, according to an updated analysis of the phase 2 JAKARTA2 study.

Treatment with fedratinib may lead to clinically meaningful responses among patients with the blood cancer myelofibrosis who were previously treated with Jakafi (ruxolitinib), according to an updated analysis of the phase 2 JAKARTA2 study.

For those with myelofibrosis — a group of rare cancers in which bone marrow is progressively replaced by scar tissue so that it can’t generate healthy blood cells – a gap in treatment exists given the fact that there are very limited options for curative treatment. “We currently only have one curative treatment, which is allogeneic stem cell transplantation, for which only 5% to 10% of patients are eligible for. The vast majority of patients don’t have a curative treatment, and even allogeneic stem cell transplantation cures about 50% of patients and carries a big risk,” explained study author Dr. Claire N. Harrison, deputy clinical director of cancer and hematology at Guy’s and St. Thomas’ NHS Foundation Trust Hospital in London.

“Current treatments prolong life, but only by a short amount of time. Many patients will fail those treatments,” she added. “…We really need to find something that is helpful to those patients.”

Fedratinib is a highly selective JAK2 inhibitor, a new member of an existing class of drugs. It works by inhibiting the activity of STAT 3 and 5 proteins, which slows the growth of, and may kill, cancer cells.

Previously, researchers were conducting the multicenter, open label, single-arm phase 2 JAKARTA2 study that evaluated the efficacy of fedratinib in 97 patients who were previously treated with Jakafi. However, the trial was placed on clinical hold in 2013.

The hold was lifted in August 2017, and now, researchers are recruiting patients for the FREEDOM studies — designed to evaluate the JAK2 inhibitor as treatment for patients with primary, post-polycythemia vera or post-essential thrombocythemia myelofibrosis. With this, Harrison and colleagues conducted an updated analysis of the JAKARTA2 trial to “use the knowledge we now have about myelofibrosis and reclassify the patients and very carefully look at the responses that these patients had,” Harrison said.

In their analysis, the researchers found that patients who failed on prior Jakafi treatment responded well to fedratinib: 31% of patients exhibited a 35% or greater reduction in spleen volume at the end of the sixth cycle of treatment and the proportion of patients who exhibited a 50% or greater symptom response rate was 27%.

The most common hematologic abnormalities from treatment with fedratinib were anemia (64%) and thrombocytopenia (24%), while non-hematologic side effects were diarrhea (62%), nausea (56%), vomiting (41%), and constipation (21%).

“This is really important because it shows that looking back and with our current 2019 study, we still saw something significant for our patients,” Harrison said. “Using that data means we can hopefully bring fedratinib to patients in clinics in the future.”

Enrollment for the FREEDOM studies is ongoing. In the United States, the Food and Drug Administration (FDA) is set to make a decision on the drug’s approval by Sept. 3.

“The acceptance of the (new drug application) and granting of priority review for fedratinib represent the first potential new treatment option after many years for patients affected by myelofibrosis,” Dr. Jay Backstrom, chief medical officer for Celgene — the drug’s manufacturer – said in a release announcing the FDA’s action on March 5.

“Patients with myelofibrosis, including the number who are ineligible for (or whose disease progressed while taking) existing therapy continues to increase, representing a well-defined unmet medical need,” he added. “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.”