Incyte Corporation,  a Wilmington, Delaware-based biopharmaceutical company focused on developing and commercializing proprietary small molecule drugs for oncology and inflammation, said that the US Food and Drug Administration (FDA) has granted marketing approval for Jakafi (ruxolitinib) 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 per cent of MF patients.

Jakafi (JAK-ah-fye) is the first and only product to be approved by the FDA for MF, and the first in a new class of drugs, known as JAK inhibitors, to be approved for any indication. Jakafi is an oral JAK1 and JAK2 inhibitor.

“The availability of Jakafi is a significant medical advancement for people living with myelofibrosis, a debilitating disease,” stated Paul A Friedman, MD, president and chief executive officer of Incyte. “This milestone marks a tremendous achievement for Incyte because a scientific discovery from our research laboratories has become the first JAK inhibitor to reach the market and provide a clinical benefit to patients.”

MF is a progressive, potentially life-threatening blood cancer with limited treatment options. Patients with MF suffer a high disease burden characterized by bone marrow failure, enlarged spleen (splenomegaly) and debilitating symptoms including fatigue, severe itching (pruritus), night sweats, bone pain, and early satiety (a feeling of fullness), leading to impaired quality of life. The enlarged spleen and debilitating symptoms of MF are linked to dysregulated signalling in the Janus kinase (JAK) pathway.

“Today’s FDA approval of Jakafi has the potential to transform the way we treat myelofibrosis,” said Srdan Verstovsek, MD, PhD, associate professor, Department of Leukaemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Centre and the principal investigator of the COMFORT-I pivotal trial. “In this phase III 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.”

“We are very excited about the first FDA approval of a treatment for MF. Not only is this a new therapy, but it brings additional education, awareness and attention to a profoundly debilitating disease,” stated Robert Rosen, president of MPN Research Foundation.

The FDA approval was based on results from two randomized phase III 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 six 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 parameters.

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 endpoint, 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 (p<0.0001). A 35% reduction in spleen volume correlates to approximately a 50% reduction in spleen size on palpation. At week 24, the percentage of patients with a greater than or equal to 50% improvement in the TSS was 45.9% and 5.3% in patients treated with Jakafi and placebo, respectively (p<0.0001), with a median time to response of less than four weeks.

The COMFORT-II trial, conducted by Novartis, Incyte’s collaboration partner outside of the US, 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 endpoint, 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<0.0001).

Incyte entered into a worldwide collaboration and license agreement with Novartis. Incyte retained exclusive rights for the development and commercialization of ruxolitinib (INCB424) in the United States. Novartis received exclusive rights to the development and potential commercialization of ruxolitinib in all haematology-oncology indications outside of the United States.