Incyte Corporation (Nasdaq:INCY) - Results from a Phase I/II study of Incyte's janus kinase (JAK) inhibitor with the investigational name INCB18424 (also known as INCB018424 and INC424) were published today in The New England Journal of Medicine, demonstrating marked and durable clinical benefits in patients with myelofibrosis. Incyte retained rights for the development and potential commercialization of INCB18424 in the US and out-licensed the compound to Novartis for development and potential commercialization outside the US.
“The rapid and durable clinical benefits observed in patients in this study signify a major step forward in our understanding of this serious condition and provide compelling evidence that INCB18424 has the potential to be the first targeted treatment for myelofibrosis.”
Myelofibrosis is a rare, life-threatening hematological neoplasm characterized by bone marrow failure, enlarged spleen (splenomegaly), debilitating symptoms, poor quality of life, weight loss and shortened survival. There are no approved medical treatments in the US for the disease. Both the US Food and Drug Administration and European Medicines Agency have granted INCB18424 orphan drug status for myelofibrosis.
"Effective therapies are needed for patients with myelofibrosis, which is very debilitating and life threatening," said lead investigator Srdan Verstovsek, MD, PhD, of M.D. Anderson Cancer Center, Houston, Texas. "The rapid and durable clinical benefits observed in patients in this study signify a major step forward in our understanding of this serious condition and provide compelling evidence that INCB18424 has the potential to be the first targeted treatment for myelofibrosis."
The Phase I/II study of 153 patients showed that 70% to 82% of myelofibrosis patients receiving oral INCB18424 twice daily experienced marked (25% or more) reduction in palpable spleen size which was durable for more than one year of follow-up. More than half of subjects treated with an optimized dose regimen which began with 15 mg twice daily achieved at least a 50% reduction in palpable spleen size. This marked reduction was confirmed using objective measurements by MRI, where 48% of patients on optimized regimens had at least a 35% reduction in spleen volume.
After only one month of therapy, patients with symptoms including fatigue, night sweats and pruritus (itching) achieved more than 50% improvement in symptom scores, as measured by the Myelofibrosis Symptom Assessment Form. Patients, particularly those with prior weight loss, experienced a clinically meaningful gain in total body weight following treatment. Additional clinical benefits observed in the study included improved performance status, increased exercise capacity, and normalization of elevated platelet and white cell counts. These improvements were accompanied by reductions of circulating cytokines, inflammation-causing proteins in the blood that are markedly elevated in patients with myelofibrosis1.
Two Phase III clinical trials, COMFORT-I in the US, Canada and Australia, and COMFORT-II in Europe, have completed enrollment and are evaluating the benefits of treatment with INCB18424 compared to either placebo or best available care2.
A strong association exists between abnormal JAK signaling and the development of myelofibrosis, polycythemia vera, and essential thrombocythemia, a related group of conditions referred to as myeloproliferative neoplasms3-6. Patients with these diseases can progress to secondary acute myelogenous leukemia7, which is virtually untreatable and is associated with a dismal prognosis8. The discovery of JAK mutations common to myelofibrosis, polycythemia vera and essential thrombocythemia, has linked them on a molecular level9. This finding, together with the fact that these patients tend to have elevated inflammatory cytokines that signal through JAK1 and JAK2, led Incyte to the discovery and development of INCB18424, a potent, selective inhibitor of the JAK1 and JAK2 tyrosine kinases.
"The results of this study support the overall scientific promise of JAK1 and JAK2 inhibition in the treatment of myeloproliferative neoplasms, with clinical improvement demonstrated for the first time in the treatment of myelofibrosis," stated Paul A. Friedman, Chief Executive Officer and President of Incyte.