FDA approves first drug to treat a rare bone marrow disease

FDA approved ruxolitinib (Jakafi, Incyte) for the treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF.

Patients with intermediate and high-risk MF represent 80% to 90% of MF patients. Jakafi is the first and only product to be approved by FDA for MF, and the first in a new class of drugs, known as JAK (Janus Associated Kinase) inhibitors, to be approved for any indication. Jakafi is an oral JAK1 and JAK2 inhibitor. It is a tablet taken 2 times a day.

MF is a disease in which the bone marrow is replaced by scar tissue resulting in blood cells being made in organs such as the liver and the spleen. This disease is marked by an enlarged spleen, anemia, decreased white blood cells and platelets, and myelofibrosis-related symptoms.

Symptoms include fatigue, abdominal discomfort, pain under the ribs, feeling full (satiety), muscle and bone pain, itching, and night sweats.

FDA approval was based on results from 2 randomized phase 3 trials (COMFORT-I and COMFORT-II), which demonstrated that patients treated with Jakafi experienced significant reductions in splenomegaly (enlarged spleen). COMFORT-I also demonstrated improvements in symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) v.2.0 electronic diary and the MFSAF Total Symptom Score (TSS) comprised of 6 specific symptoms (abdominal discomfort, pain under the left ribs, an early feeling of fullness, night sweats, bone and muscle pain, and itching) all of which contributed to the overall benefit. Most patients taking placebo experienced worsening of these same symptoms.

The COMFORT-I trial, conducted by Incyte, compared Jakafi to placebo in 309 patients with primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF. The trial met the primary end point, showing that 41.9% of patients treated with Jakafi experienced a 35% or greater reduction in spleen volume at 24 weeks, compared with 0.7% of patients taking placebo (PP

The COMFORT-II trial, conducted by Novartis, Incyte’s collaborative partner outside of the United States, compared Jakafi to best available therapy in 219 patients with primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF. This trial also met the primary end point, showing that 28.5% of patients treated with Jakafi experienced a 35% or greater reduction in spleen volume at 48 weeks, compared with 0% of patients in the best available therapy arm (P

The most common adverse reactions in both studies were thrombocytopenia and anemia. These events were manageable and rarely led to discontinuation of Jakafi treatment. The most common non-hematologic adverse reactions were bruising, dizziness, and headache.

“[The] FDA approval of Jakafi has the potential to transform the way we treat myelofibrosis,” Srdan Verstovsek, MD, PhD, associate professor, department of leukemia, division of cancer medicine, The University of Texas MD Anderson Cancer Center and the principal investigator of the COMFORT-I pivotal trial, said in an Incyte press release. “In this phase 3 clinical trial, 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.”