FDA Approves Ruxolitinib, First Drug Ever for Myelofibrosis

Zosia Chustecka

November 16, 2011

November 16, 2011 — The first drug treatment ever for myelofibrosis, ruxolitinib (Jakafi, Incyte Corp), was approved today by the US Food and Drug Administration (FDA).

The drug was approved ahead of schedule under the FDA's priority review program for products that offer a significant advance over available therapies or provide a treatment where no adequate therapy exists. It has been designated an orphan drug, meaning that the disease affects fewer than 200,000 people in the United States.

Myelofibrosis, a rare disease of the bone marrow, is associated with the dysregulation of 2 enzymes — janus-associated kinase (JAK)1 and 2 — which are involved in regulating blood and immunologic functioning. As the disease progresses, bone marrow is replaced with scar tissue, leading to anemia and thrombocytopenia. However, the scarred bone marrow tissue accumulates in other organs, most notably in the spleen and the liver.

Ruxolitinib, an oral drug taken twice daily, inhibits JAK1 and 2. It is the first JAK inhibitor to be approved. In 2 pivotal clinical trials that were submitted for the approval, treatment with the drug led to a significant reduction in symptoms, including a significant reduction in the enlarged spleen of these patients, as reported earlier this year at the American Society of Clinical Oncology annual meeting.

"This therapy has the potential to change the treatment landscape," principal investigator Allessandro Vannucchi, MD, associate professor of hematology at the University of Florence, Italy, said at the time. "We've urgently needed new treatments for this condition," he added.

Commenting on the approval of the drug, Richard Pazdur, MD, the FDA's director of oncology products, said that ruxolitinib "represents another example of an increasing trend in oncology where a detailed scientific understanding of the mechanisms of a disease allows a drug to be directed toward specific molecular pathways."

Clinical Trial Results

"The clinical trials leading to this approval focused on problems that patients with myelofibrosis commonly encounter, including enlarged spleens and pain," Dr. Pazdur explained.

The 2 trials enrolled a total of 538 patients who were resistant or refractory to available treatment or were ineligible for allogeneic bone marrow transplantation. All patients had enlarged spleens and were in need of treatment as a result of disease-related symptoms, according to the FDA announcement.

Patients in the studies received ruxolitinib, placebo, or the best available therapy (hydroxyurea or glucocorticoids). A greater percentage of patients receiving ruxolitinib experienced a more than 35% reduction in spleen size, compared with patients receiving placebo or best available therapy. Similarly, a greater proportion of patients receiving ruxolitinib had a more than 50% reduction  in myelofibrosis-related symptoms — including abdominal discomfort, night sweats, itching, and bone or muscle pain — than those receiving placebo, according to the FDA.

The most serious adverse effects in patients treated with ruxolitinib were thrombocytopenia, anemia, fatigue, diarrhea, dyspnea, headache, dizziness, nausea, and confusion.

"Today's FDA approval of ruxolitinib has the potential to transform the way we treat myelofibrosis," said Srdan Verstovsek, MD, PhD, from the University of Texas M.D. Anderson Cancer Center in Houston, who was the principal investigator on 1 of the 2 trials. "We observed significant reductions in spleen size and significant improvements in symptoms. Importantly, these benefits were achieved early on — most within a month — and tended to be durable during treatment. In contrast, most of the patients who received placebo saw their spleens increase and their symptoms worsen," he said in a statement.

Ruxolitinib is approved for use in patients with intermediate or  high-risk myelofibrosis, which represents 80% to 90% of all patients with myelofibrosis, the manufacturer noted.


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