COMFORT-II, the second pivotal phase III trial of Incyte Corporation's investigational Janus kinase (JAK) inhibitor, ruxolitinib (INCB18424 or INC424), has met its primary endpoint of significantly reducing spleen size in patients with Myelo-Fibrosis (MF), when compared to best available therapy. This trial was conducted by Novartis as part of the Incyte-Novartis worldwide collaboration and license agreement for ruxolitinib, an oral JAK1 and JAK2 inhibitor.

The European study, called COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy), showed treatment with ruxolitinib provided a statistically significant reduction in spleen size in patients with primary MF, Post-Polycythemia Vera Myelo-Fibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelo-Fibrosis (PET-MF), when compared with best available therapy, administered at doses and schedules determined by the investigator. The safety profile of ruxolitinib was consistent with previous studies. Complete study data will be submitted to an upcoming medical meeting.

“The positive results from the European COMFORT-II trial confirm the data from the US trials and further strengthen our confidence that ruxolitinib has the potential to provide myelofibrosis patients, and the physicians who treat them, a new approach to effectively manage this debilitating, life-threatening disease,” stated Paul Friedman, MD, president and CEO of Incyte. “We and Novartis will continue to work diligently to bring ruxolitinib forward as the first JAK1 and JAK2 inhibitor available to treat MF.”

Data from the COMFORT-II and COMFORT-I clinical trials will form the basis of worldwide regulatory filings, planned to begin in the second quarter of 2011, first in the US followed by the EU. Both the European Commission (EC) and the United States Food and Drug Administration (FDA) have granted ruxolitinib orphan drug status for MF.

“The COMFORT-I and II trials constitute the largest clinical trial program to date in myelofibrosis. Data from these two phase III trials demonstrate how treatment with ruxolitinib was more effective than placebo and any other available medical therapies,” said Richard Levy, MD, executive vice president and Chief Drug Development and Medical Officer of Incyte. “It is also very gratifying to see that the COMFORT-II safety profile is consistent with the previous studies.”

COMFORT-II is a randomized, open-label phase III study of ruxolitinib (also known as INCB18424 or INC424) versus best available therapy that enrolled 219 patients with primary MF, PPV-MF or PET-MF in 56 study locations in Europe. Two-thirds received ruxolitinib and one-third received best available therapy, administered at doses and schedules determined by the investigator.

The primary endpoint for COMFORT-II is the proportion of patients achieving a reduction in spleen volume of 35% or more from baseline to week 48 as measured by MRI (or CT scan in applicable patients). Reduction of spleen size is an accepted measurement for clinical improvement in MF1. COMFORT-II is sponsored by Novartis5.

MF is an uncommon, life-threatening blood cancer characterized by bone marrow failure, enlarged spleen (splenomegaly), debilitating symptoms including fatigue, night sweats and pruritus, poor quality of life, and weight loss, as well as shortened survival. MF is one of the Philadelphia chromosome-negative Myelo-Proliferative Neoplasms (MPNs) which also includes polycythemia vera and essential thrombocythemia.

Of the JAK-associated MPNs, MF carries the greatest risk of a poor prognosis, including transformation to fatal acute myelogenous leukemia, and there are currently no approved treatments for MF in the US. Although allogeneic stem cell transplantation may cure MF, the procedure is associated with significant morbidity and mortality and is usually appropriate only in younger patients.

Ruxolitinib is Incyte's lead internally developed JAK1 and JAK2 inhibitor that entered phase I clinical testing in May 2007 and has shown clinical activity in a number of haematology and inflammatory conditions. The compound recently completed a phase III programme in myelofibrosis and is currently in a global phase III registration trial, RESPONSE, in patients suffering from advanced polycythemia vera and a Phase II trial in patients with acute leukaemias. Additional clinical studies evaluating ruxolitinib in other haematologic cancers and malignant diseases such as lymphoma and pancreatic cancer are planned for 2011.