The largest clinical program to date in patients with a potentially life-threatening blood cancer known as myelofibrosis (MF) has shown that a new therapeutic candidate, ruxolitinib (INCB-018424, Incyte Corp /Novartis AG), provided clinical benefits to patients compared to placebo and best available therapy.

Ruxolitinib was initially developed to target the constitutive activation of the JAK-STAT pathway in patients with myeloproliferative neoplasms (MPNs), previously referred to as myeloproliferative disorders (MPDs)which also include essential thrombocythemia and polycythemia vera. However, ongoing research showed meaningful reductions in spleen size and relief of debilitating symptoms have been noted in patients in patients with myelofibrosis (MF) in both primary and post-essential thrombocythemia (PET-MF)/ and post-polycythemia vera (PPV-PV).

A life threatening blood cancer
Myelofibrosis (MF), the most serious of the myeloproliferative neoplasms (MPNs), is a potentially life threatening blood cancer, characterized by bone marrow fibrosis (“scar tissue”) and splenomegaly (huge spleen), as well as anemia and/or thrombocytopenia, and constitutional symptoms such as pruritus, fatigue, night sweats, fever, weight loss and bone pain.

Median survival in MF is less than 6 years but can be as little as 27 months in high-risk patients. There are currently no FDA-approved medicines for the disease.

Trial results
Results of the trial were presented by Srdan Verstovsek,MD, PhD, Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, at the 16th Congress of EHA from the COMFORT-I study, one of two pivotal studies demonstrating statistical significance in achieving primary and secondary efficacy endpoints, including reduction of spleen size and improvement in multiple symptoms. The second Phase III study, COMFORT-II, is also being presented at EHA. COMFORT-I was conducted in the U.S., Canada and Australia; COMFORT-II in the EU.

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Commenting on the trial results, Verstovsek said: ?The ruxolitinib clinical data establish a benchmark for a new therapeutic approach to decrease splenomegaly, itself associated with significant morbidity, and to improve the symptoms that have such a profound impact on the quality of life for patients with myelofibrosis. These benefits are clinically meaningful and directly relate to the significant improvements we saw in the global health status of patients receiving ruxolitinib.?

?The lack of response in the placebo group in COMFORT-I and in the best available therapy arm of COMFORT-II highlights the need for new therapeutic options to reduce spleen size and decrease symptoms, such as fatigue and weight loss, in patients with MF,? Verstovsek added.

Well tolerated treatment
In addition to the efficacy findings, ruxolitinib was shown to be well-tolerated, with approximately three-quarters of patients still on active therapy following completion of the clinical program. The most common adverse events seen were anemia and thrombocytopenia (low platelet counts), both of which were manageable.

Other study programs
Ruxolitinib also is being evaluated in a global Phase III study (RESPONSE) in patients with another MPN, advanced polycythemia vera, who are resistant to or intolerant of the cytostatic agent hydroxyurea. The invesyigational agent is also being evaluated in various other hematologic malignancies.

For more information:
– Passamonti F, Maffioli M, Caramazza D,Cazzola M. yeloproliferative neoplasms: From JAK2 mutations discovery to JAK2 inhibitor therapies. Oncotarget. 2011 Jun 5. [Epub ahead of print][Full Article]
– Naqvi K, Verstovsek S, Kantarjian H, Ravandi F. A potential role of ruxolitinib in leukemia. Expert Opin Investig Drugs. 2011 Jun 3. [Epub ahead of print]
– Mesa RA, Kantarjian H, Tefferi A, Dueck A, Levy R,et al. Evaluating the serial use of the myelofibrosis symptom assessment form for measuring symptomatic improvement: Performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Cancer. 2011 Apr 8. doi: 10.1002/cncr.26129. [Epub ahead of print]

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