Incyte Announces Ruxolitinib (INC424) Shows Significant Clinical Benefit for Myelofibrosis Patients in Two Phase III Studies at

Incyte Announces Ruxolitinib (INC424) Shows Significant Clinical Benefit for Myelofibrosis Patients in Two Phase III Studies at ASCO Annual Meeting
A potentially life-threatening blood cancer with limited treatment options, myelofibrosis is characterized by bone marrow failure, enlarged spleen and highly debilitating symptoms
Both Phase III studies, COMFORT-I conducted by Incyte and COMFORT-II conducted by Novartis, met their primary efficacy endpoint and provide the basis for US and EU filings in June
Highlights from the ruxolitinib clinical program are being reported at ASCO in a press briefing on Saturday, June 4;further data to be reported in two oral presentations on Monday, June 6
Incyte to host a webcast for investors featuring these results onMonday, June 6 at 7:00 p.m. CT

CHICAGO, Jun 04, 2011 (BUSINESS WIRE) --

Incyte Corporation (Nasdaq:INCY) announced today results from the global, pivotal Phase III clinical program of ruxolitinib (INCB18424 or INC424) in patients with myelofibrosis (MF) at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting. MF is a potentially life-threatening blood cancer characterized by bone marrow failure, enlarged spleen (splenomegaly) and debilitating symptoms. MF has a poor prognosis and limited treatment options.1,2 The Phase III studies, COMFORT-I and COMFORT-II, were conducted as part of the Incyte-Novartis worldwide collaboration and license agreement for ruxolitinib, Incyte's lead oral JAK1 and JAK2 inhibitor.


Ruxolitinib-treated patients experienced significant reductions in splenomegaly and improvement in symptoms and overall quality of life measures while patients in the control arms, (placebo and best available therapy [BAT]), experienced progressive splenomegaly and worsening of symptoms.


The COMFORT-I (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Treatment) study met the primary efficacy endpoint, showing that 41.9% of ruxolitinib-treated patients experienced a 35% or greater reduction in spleen volume at 24 weeks as measured by magnetic resonance imaging (MRI), or computed tomography (CT), compared with 0.7% of patients in the placebo arm (p<0.0001). The vast majority of ruxolitinib-treated patients had some reduction in spleen volume with a median reduction of 33%. In addition, the COMFORT-I study showed statistically significant, clinically meaningful improvements of symptoms, a key secondary efficacy endpoint.3
The COMFORT-II study demonstrated that ruxolitinib produced a volumetric spleen size reduction of 35% or greater in 28.5% of myelofibrosis patients compared to 0% of patients in the BAT arm at 48 weeks (p<0.0001). The trial also met the key secondary endpoint, with 31.9% of ruxolitinib-treated patients demonstrating a 35% or greater volumetric spleen size reduction compared to 0% in the BAT arm at week 24 (p<0.0001). Additional data based on EORTC Quality of Life Questionnaire (EORTC QLQ-C30) scores showed a marked improvement in overall quality of life measures, functioning and symptoms relative to the BAT arm.4

"The positive results seen in these two pivotal trials support ruxolitinib as an important advance for patients with myelofibrosis for which there are limited effective treatments," stated Paul Friedman, M.D., President and CEO of Incyte. "We and Novartis continue to work diligently with health authorities to bring ruxolitinib forward as the first JAK1 and JAK2 inhibitor available to treat these patients."

"In its entirety, the efficacy data from COMFORT-I and COMFORT-II have the potential to establish ruxolitinib as a new therapeutic approach by decreasing splenomegaly, itself associated with significant morbidity, and improving the symptoms that have such a profound impact on the quality of life for patients with myelofibrosis," said Srdan Verstovsek, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center and principal investigator for the COMFORT-I trial. "By contrast, patients treated with placebo or best available care experienced progressive splenomegaly and symptomatology."

About COMFORT-I

COMFORT-I is a randomized (1:1), double-blind, placebo-controlled Phase III study comparing the efficacy and safety of ruxolitinib to placebo in 309 patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) and involved 89 clinical sites in the US, Canada and Australia.

The primary endpoint was the proportion of patients achieving a reduction in spleen volume of 35% or more from baseline to week 24 as measured by MRI (or CT scan in applicable patients). Key secondary endpoints included duration of maintenance of a 35% or greater reduction in spleen volume from baseline and the proportion of patients with 50% or more reduction in symptom improvement as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) version 2.0 electronic diary.

Beyond the significant reductions in spleen volume described earlier, ruxolitinib-treated patients also experienced a rapid and sustained improvement in MF-associated symptoms as measured by the modified MFSAF electronic diary. At week 24, the proportion of patients with 50% or greater improvement in Total Symptom Score (TSS) was 45.9% vs 5.3% (ruxolitinib-treated vs. placebo) (p<0.0001). Also, at week 24, the mean percent improvement in TSS in ruxolitinib-treated patients was 46.1%, in contrast to a worsening in TSS of 41.8% in the placebo arm (p<0.0001). The majority of responders had achieved a response within the first 4 weeks.3

These clinical benefits associated with ruxolitinib were seen in patients with or without the JAK2V617F mutation.

COMFORT-I was conducted by Incyte.

About COMFORT-II

COMFORT-II is a randomized (2:1), open-label Phase III study of ruxolitinib versus BAT that enrolled 219 patients with primary MF, PPV-MF or PET-MF in 56 study locations in Europe.

The primary endpoint was the proportion of patients achieving a reduction in spleen volume of 35% or greater from baseline to week 48 as measured by MRI (or CT scan in applicable patients). Secondary endpoints included spleen size reduction at 24 weeks, duration of spleen size reduction, change in bone marrow histomorphology, leukemia-free survival, progression-free survival and overall survival. Median survival has not yet been achieved. Patients continue to receive ruxolitinib therapy and to be followed to determine longer-term outcomes.4

COMFORT-II was conducted by Novartis.

About Safety

COMFORT-I and COMFORT-II confirmed ruxolitinib was well-tolerated by MF patients.

In COMFORT-I the most common clinical adverse events, reported by the investigators, of any grade in more than 20% of patients receiving ruxolitinib were: thrombocytopenia (34.2% vs 9.3% for placebo), anemia (31.0% vs 13.9%), fatigue (25.2% vs 33.8%), and diarrhea (23.2% vs 21.2%). Based on laboratory assessments, the percentage of patients with grade 3 or 4 low platelet counts at any time during the study was 12.9% on ruxolitinib vs 1.3% on placebo. The percentage of patients with grade 3 or 4 low hemoglobin values at any time during the study was 45.2% on ruxolitinib vs 19.2% on placebo. Only one patient in each arm discontinued for thrombocytopenia and only one in each arm for anemia. The rates of grade 3 and 4 thrombocytopenia and anemia in patients receiving ruxolitinib decreased over the 24 weeks of the study and became approximately equal to the rates with patients on placebo. Comparable clinical benefit (spleen volume reduction and improvement in total symptom score) was seen in ruxolitinib-treated patients with or without grade 3 or 4 anemia whereas placebo-treated patients had worsening of these endpoints, especially those patients with grade 3 or 4 anemia.3

In COMFORT-II for patients in the ruxolitinib arm, the most commonly reported grade 3 or higher adverse events were hematologic. Based on laboratory assessments, the percentage of patients with grade 3 or 4 low platelet counts at any time during the study was 8.3% on ruxolitinib vs 7.2% on BAT. The percentage of patients with grade 3 or 4 low hemoglobin values at any time during the study was 42.4% on ruxolitinib vs 31.4% on BAT. Only one patient in each arm discontinued for thrombocytopenia and no patient discontinued for anemia. The most commonly reported grade 3 or higher non-hematologic adverse events in the ruxolitinib arm were abdominal pain (3.4% vs 2.7% in the BAT arm), back pain (2.1% vs 0%), weight gain (2.1% vs 0%), and fever (2.1% vs 0%). Only 8.2% and 5.5% of patients discontinued the study because of an adverse event in the ruxolitinib and BAT arms, respectively.4

COMFORT-I and COMFORT-II Presentations at ASCO

In addition to the data described during the press briefing, further data from the ruxolitinib clinical program will be reported in oral scientific presentations on Monday, June 6:


Abstract #6500 (9:30 a.m. CT): COMFORT-I results presented by Srdan Verstovsek, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.
Abstract #LBA6501 (9:45 a.m. CT): COMFORT-II results presented by Alessandro M. Vannucchi, M.D.,Professor of Hematology, Director of the Specialty School in Hematology, University of Florence, Italy.

Results of the COMFORT clinical trials will also be presented at the 16th Congress of the European Hematology Association (EHA) from June 9-12 in London.

About Myelofibrosis (MF)

Myelofibrosis is a potentially life-threatening blood cancer characterized by bone marrow failure, enlarged spleen (splenomegaly) and debilitating symptoms, such as fatigue, pruritus, night sweats, bone pain and early satiety. MF is one of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which also include polycythemia vera and essential thrombocythemia. Aberrant activation of the Janus kinase (JAK) pathway, which regulates blood cell production, has been associated with the development of the MPNs, including MF.5

Myelofibrosis has a poor prognosis and can lead to shortened survival. Within 10 years of diagnosis, up to 20% of patients experience transformation to fatal secondary acute myelogenous leukemia. There are limited treatment options and no FDA-approved medicines for MF; the only potential cure is allogeneic stem cell transplant (appropriate for a very small subset of patients, mostly younger in age).1

About Ruxolitinib (INCB18424/INC424)

Ruxolitinib is Incyte's lead internally developed JAK1 and JAK2 inhibitor that entered clinical testing in May 2007 and has shown clinical activity in a number of hematology conditions. The compound recently completed a global Phase III program in myelofibrosis and is currently in a global Phase III registration study, RESPONSE, in patients suffering from advanced polycythemia vera,6 as well as Phase II studies in patients with other hematologic malignancies and solid tumors. Additional clinical studies evaluating ruxolitinib in patients with lymphoma and pancreatic cancer are planned for 2011.

About the Ruxolitinib Incyte-Novartis Collaboration

Under the terms of the 2009 Incyte and Novartis worldwide collaboration and license agreement, Incyte retained exclusive rights for the development and potential commercialization of ruxolitinib in the US. Novartis received exclusive rights to the development and potential commercialization of ruxolitinib in all hematology-oncology indications outside of the US.

Data from the COMFORT-I and COMFORT-II clinical studies will form the basis of worldwide regulatory filings. Both the European Commission and the US Food and Drug Administration have granted ruxolitinib orphan drug status for myelofibrosis.

About the Webcast

Incyte will host a webcast for investors at the ASCO meeting on Monday, June 6 at 7:00 p.m. CT. During the webcast, Drs. Verstovsek and Vannucchi will review the data presented during the ASCO sessions. The live webcast can be accessed by going to Incyte's website at www.incyte.com under Investor Relations, Events and Webcasts. A replay of the webcast will also be available following the event.

About Incyte

Incyte Corporation is a Wilmington, Delaware-based drug discovery and development company focused on developing proprietary small molecule drugs for oncology and inflammation. For additional information on Incyte, visit the Company's web site at www.incyte.com.

Forward-Looking Statements

Except for the historical information contained herein, the matters set forth in this press release, including statements regarding the positive results seen in the two pivotal trials COMFORT-I and COMFORT-II supporting ruxolitinib as an important advance for patients with myelofibrosis for which there are limited effective treatments, Incyte and Novartis continuing to work diligently with health authorities to bring ruxolitinib forward as the first JAK1 and JAK2 inhibitor available to treat these patients, the efficacy data from COMFORT-I and COMFORT-II having the potential to establish ruxolitinib as a new therapeutic approach by decreasing splenomegaly and improving symptoms for patients with myelofibrosis, further data from the ruxolitinib clinical program being reported in oral scientific presentations and a subsequent webcast on Monday, June 6, results of the COMFORT clinical trials also being presented at the 16th Congress of the European Hematology Association from June 9-12 in London, additional clinical studies evaluating ruxolitinib in patients with lymphoma and pancreatic cancer being planned for 2011 and data from the COMFORT-I and COMFORT-II clinical studies forming the basis of worldwide regulatory filings are all forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995.

These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the high degree of risk and uncertainty associated with drug development and clinical studies, unanticipated developments in the efficacy or safety of ruxolitinib, the possibility that the outcomes for each of the planned clinical studies for ruxolitinib may not be favorable, the possibility that regulatory authorities may require additional clinical studies in order to support registration of ruxolitinib in any particular indication, the possibility that there may be other interpretations of the data produced in one or more of Incyte's clinical studies, the risk that regulatory authorities will require more extensive data for the ruxolitinib regulatory filings than currently expected, future competitive or other market factors that may adversely affect the commercial potential for ruxolitinib, the results of further research and development, and other risks detailed from time to time in Incyte's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2011. Incyte disclaims any intent or obligation to update these forward-looking statements.

References


The Leukemia & Lymphoma Society. Idiopathic Myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis. Accessed May 2011.
Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33:1199-1203.
Verstovsek S., Morgan G. Results of COMFORT- I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) vs placebo (PB) for patients with myelofibrosis (MF). Abstract #6500. 2011 American Society of Clinical Oncology Annual Meeting.
Harrison CN. Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) vs best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF). Abstract #LBA6501. 2011 American Society of Clinical Oncology Annual Meeting.
Vannucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59:171-191.
National Institutes of Health. Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: The RESPONSE Trial. Available at http://clinicaltrials.gov/ct2/results?term=%22The+RESPONSE+Trial%22. Accessed May 2011.

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