COMFORT-II data demonstrate that patients with myelofibrosis treated
with Jakafi achieved a 33 percent reduction in the risk of death after
five years
Incyte Corporation (Nasdaq:INCY) announces data from two Phase 3 studies
evaluating the long-term safety and efficacy of Jakafi®
(ruxolitinib) in patients with Myeloproliferative Neoplasms (MPNs). In
myelofibrosis (MF), results of a five-year follow-up from the COMFORT-II
study demonstrate a continued survival benefit in patients originally
randomized to ruxolitinib compared with patients randomized to best
available therapy (BAT), with a 33 percent reduction in the risk of
death (HR, 0.67; 95%CI, 0.44-1.02; P=.06). Because patients in
the BAT arm had crossed over to receive ruxolitinib therapy (median 17
months after randomization), these data may suggest that earlier
treatment with ruxolitinib may be associated with improved long-term
survival in patients with intermediate-2 or high-risk MF. Additionally,
53 percent of patients treated with ruxolitinib (n=78/146) achieved at
least a 35 percent reduction in spleen volume from baseline that was
sustained over time (median duration 3.2 years).
“These data from the COMFORT-II study reinforce the positive and
long-term clinical benefits seen in patients with myelofibrosis who are
treated with Jakafi,” said Rich Levy, MD, Chief Drug Development
Officer, Incyte. “The reduction in the risk of death and the sustained
improvements in spleen volume are meaningful and important results for
the community of patients with this rare blood cancer.”
An analysis of the RESPONSE study is also planned for presentation at
ASH. Previously published results in the New England Journal of
Medicine showed that treatment with ruxolitinib, compared to
standard therapy improved hematocrit control and reduced spleen volume
in patients with polycythemia vera (PV) who had an inadequate response
to or had unacceptable side effects from hydroxyurea (HU). The data at
ASH demonstrate that in patients with elevated white blood cell (WBC)
counts at baseline, a greater proportion of patients in the ruxolitinib
treatment arm (45%) achieved normalization of their WBC counts
(achieving a WBC ≤10×109/L or a ≥50% reduction from baseline)
compared to BAT (22%) or HU (9%) at week 32.
These data are scheduled for presentation at the 57th
American Society of Hematology Annual Meeting taking place December 5-8,
2015 in Orlando, FL.
Results from the COMFORT-II Study
Data from a five-year follow-up of the COMFORT-II trial, a randomized,
open-label Phase 3 study evaluating long-term safety and efficacy of
ruxolitinib in patients with intermediate-2 or high-risk primary
myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis, allowing
crossover from the BAT arm to ruxolitinib after 48 weeks upon
protocol-defined progression, revealed that 53 percent of patients
treated with ruxolitinib (n=78/146) achieved at least a 35 percent
reduction in spleen volume from baseline while on treatment during the
study. Additionally, approximately one-third of evaluable JAK2
V617F-positive patients had more than a 20 percent reduction in allele
burden at 3.2 years (38%) and 3.7 years (31%). Patients treated with
ruxolitinib also experienced improvements in bone marrow fibrosis
(15.8%) with 32.2 percent reporting stable fibrosis scores.
Overall, 59 (40%) and 35 (48%) deaths were reported in the ruxolitinib
and BAT arms, respectively. Median overall survival (OS) was not reached
in the ruxolitinib arm and was 4.1 years in the group of patients
originally receiving BAT. There was a 33 percent reduction in risk of
death with ruxolitinib (HR, 0.67; 95 percent CI, 0.44-1.02; P=.06).
The estimated probability of survival at 5 years was 56 percent with
ruxolitinib and 44 percent with patients originally receiving BAT. At
week 48, BAT patients were allowed to cross over to receive ruxolitinib
upon protocol-defined progression and after week 48 all BAT patients,
irrespective of their progression status, were allowed to crossover to
receive ruxolitinib; therefore, a confounding effect on OS was observed.
An analysis correcting for crossover will be presented.
Adverse events (AEs) were consistent with those reported in previous
studies of ruxolitinib and there was no increase in the incidence of AEs
with longer exposure to treatment.
COMFORT-II is scheduled for presentation as an oral session by Dr.
Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, Guy’s
Hospital, Saturday, December 5, 2015, 9:30-11:30 AM EST, Room W224.
Results from the RESPONSE Study
The RESPONSE trial is a Phase 3 open-label study evaluating long-term
safety and efficacy of ruxolitinib in patients with PV compared to BAT
who had an inadequate response to or had unacceptable side effects from
HU. The analysis from RESPONSE to be presented at ASH shows that
patients who received ruxolitinib had greater mean reductions in WBC
counts compared with BAT or the HU subgroup of the BAT arm, and these
reductions were maintained over time. In patients with baseline WBC
counts ≥11×109/L, worsening WBC counts were observed in 10.8
percent of patients in the ruxolitinib arm versus 35.4 percent in the
BAT arm (P=0.0002) and 47.8 percent in the HU subgroup (P<0.0001).
In this same subgroup of patients with elevated WBC counts at baseline,
a greater proportion of patients in the ruxolitinib arm (45%) normalized
their WBC counts (achieving a WBC ≤10×109/L or a ≥50%
reduction from baseline) compared with BAT (22%) or HU (9%) at week 32.
The median time to achieve this response with ruxolitinib therapy was 8
weeks.
These data are scheduled for presentation as a poster session by Dr.
Carole Miller, Saint Agnes Cancer Institute, Monday, December 7, 2015,
6:00-8:00 PM EST, Hall A.
About Myelofibrosis
MF is part of a group of related rare blood cancers known as
myeloproliferative neoplasms (MPNs) where a patient’s bone marrow can no
longer produce enough normal blood cells, causing the spleen to enlarge1.
As a result, patients with MF may suffer from debilitating symptoms and
have a poor quality of life2. After diagnosis, patients with
MF have a decreased life expectancy, with an average survival of
approximately five to six years3. Although allogeneic stem
cell transplantation may cure MF, the procedure is associated with
significant morbidity and transplant-related mortality, and is available
to less than 5% of patients who are young and fit enough to undergo the
procedure4.
About Polycythemia Vera
Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) and is
typically characterized by elevated hematocrit, the volume percentage of
red blood cells in whole blood, which can lead to a thickening of the
blood and an increased risk of blood clots, as well as an elevated white
blood cell and platelet count5. Patients with PV who fail to
consistently maintain appropriate blood count levels, including
appropriate hematocrit levels, have an approximately four times higher
risk of major thrombosis (blood clots) or cardiovascular death6.
Patients with PV can also suffer from an enlarged spleen and a
significant symptom burden which may be attributed to thickening of the
blood and lack of oxygen to parts of the body7. These
symptoms commonly include fatigue, itching, night sweats, bone pain,
fever, and weight loss8.
Approximately 100,000 patients in the U.S. are living with PV9.
Current standard treatment for PV is phlebotomy (the removal of blood
from the body) plus aspirin. When phlebotomy can no longer control PV,
chemotherapy such as hydroxyurea, or interferon, is utilized10,11.
Approximately one in four patients with PV are considered uncontrolled12,13
because they have an inadequate response to or are intolerant of
hydroxyurea, the most commonly used chemotherapeutic agent for the
treatment of PV.
About Jakafi (ruxolitinib)
Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food
and Drug Administration, for treatment of people with polycythemia vera
(PV) who have had an inadequate response to or are intolerant of
hydroxyurea.
Jakafi is also indicated for treatment of people with intermediate or
high-risk myelofibrosis (MF), including primary MF, post–polycythemia
vera MF, and post–essential thrombocythemia MF.
Jakafi is marketed by Incyte in the United States and by Novartis as
Jakavi® (ruxolitinib) outside the United States.
Important Safety Information
Jakafi can cause serious side effects, including:
Low blood counts: Jakafi may cause your platelet, red blood cell,
or white blood cell counts to be lowered. If you develop bleeding, stop
taking Jakafi and call your healthcare provider. Your healthcare
provider will perform blood tests to check your blood counts before you
start Jakafi and regularly during your treatment. Your healthcare
provider may change your dose of Jakafi or stop your treatment based on
the results of your blood tests. Tell your healthcare provider right
away if you experience unusual bleeding, bruising, fatigue, shortness of
breath, or a fever.
Infection: You may be at risk for developing a serious infection
during treatment with Jakafi. Tell your healthcare provider if you
develop any of the following symptoms of infection: chills, nausea,
vomiting, aches, weakness, fever, painful skin rash or blisters.
Skin cancers: Some people who take Jakafi have developed certain
types of non-melanoma skin cancers. Tell your healthcare provider if you
develop any new or changing skin lesions.
The most common side effects of Jakafi include: anemia, low
platelet count, bruising, dizziness, headache.
These are not all the possible side effects of Jakafi. Ask your
pharmacist or healthcare provider for more information. Tell your
healthcare provider about any side effect that bothers you or that does
not go away.
Before taking Jakafi, tell your healthcare provider about all the
medications, vitamins, and herbal supplements you are taking and all
your medical conditions, including if you have an infection, have or had
tuberculosis (TB), or have been in close contact with someone who has
TB, have or had liver or kidney problems, are on dialysis, had skin
cancer or have any other medical condition. Take Jakafi exactly as your
healthcare provider tells you. Do not change or stop taking Jakafi
without first talking to your healthcare provider. Do not drink
grapefruit juice while on Jakafi.
Women should not take Jakafi while pregnant or planning to become
pregnant, or if breast-feeding.
Full Prescribing Information, including a more complete discussion of
the risks associated with Jakafi, is available at www.jakafi.com.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical
company focused on the discovery, development and commercialization of
proprietary therapeutics, primarily for oncology. For additional
information on Incyte, please visit the Company’s website at www.incyte.com.
Forward Looking Statements
Except for the historical information set forth herein, the matters set
forth in this press release, including statements regarding the
long-term efficacy and safety of Jakafi, contain predictions, estimates
and other forward-looking statements. These forward-looking statements
are based on the Company’s current expectations and subject to risks and
uncertainties that may cause actual results to differ materially,
including unanticipated developments and the risks related to the
efficacy or safety of the Company’s development pipeline, the results of
further research and development, the high degree of risk and
uncertainty associated with drug development, clinical trials and
regulatory approval processes, other market or economic factors and
competitive and technological advances; and other risks detailed from
time to time in the Company’s reports filed with the Securities and
Exchange Commission, including its Form 10-Q for the quarter ended
September 30, 2015. Incyte disclaims any intent or obligation to update
these forward-looking statements.
|
|
|
1
|
|
Leukemia & Lymphoma Society. “Myelofibrosis Facts.” Available at:
http://www.lls.org/sites/default/files/file_assets/FS14_Myelofibrosis_Fact%20Sheet_Final9.12.pdf.
Accessed November 2015.
|
2
|
|
Mesa RA, Schwagera 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.
|
3
|
|
Gangat N, Caramazza D, Vaidya R, et al. DIPSS-plus: A Refined
Dynamic International Prognostic Scoring System (DIPSS) for Primary
Myelofibrosis that Incorporates Prognostic Information from
Karyotype, Platelet Count and Transfusion Status. J Clin Oncol.
2011; 29:392-397.
|
4
|
|
Patriarca F, Bacigalupo A, Sperotto A, et al. Allogeneic
Hematopoietic Stem Cell Transplantation in Myelofibrosis: The
20-year Experience of the Gruppo Italiano Trapianto di Midollo Osseo
(GITMO). Haematologica. 2008;93(10):1514-1522.
|
5
|
|
Leukemia & Lymphoma Society. “Polycythemia Vera Facts.” Available
at: https://www.lls.org/sites/default/files/file_assets/FS13_PolycythemiaVera_FactSheet_final5.1.15.pdf.
Accessed November 2015.
|
6
|
|
Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular Events and
Intensity of Treatment in Polycythemia Vera. N Engl J Med.
2013;368:22-33.
|
7
|
|
National Institutes of Health. “What Are the Signs and Symptoms of
Polycythemia Vera?" Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/poly/signs.
Accessed November 2015.
|
8
|
|
Tefferi A. Polycythemia Vera and Essential Thrombocythemia: 2013
Update on Diagnosis, Risk-Stratification, and Management. Am J
Hematol. 2013;88:507-16.
|
9
|
|
Data on file. Incyte Corporation
|
10
|
|
Vannucchi AM. How I treat polycythemia vera. Blood. 2014;
124(22):3212-20
|
11
|
|
Passamonti F. How I treat polycythemia vera. Blood. 2012;
120(2):275-84.
|
12
|
|
Barosi G, Birgegard G, Finazzi G, et al. A Unified Definition of
Clinical resistance and Intolerance to Hydroxycarbamide in
Polycythaemia Vera and Primary Myelofibrosis: Results of a European
LeukemiaNet (ELN) consensus process. Br J Haematol. 2010;149:961-3.
|
13
|
|
Alvarez-Larrán A, Pereira A, Cervantes F, et al. Assessment and
Prognostic Value of the European LeukemiaNet criteria for
Clinicohematologic Response, Resistance, and Intolerance to
Hydroxyurea in Polycythemia Vera. Blood. 2012;119:1363-9
|
|
|
|
View source version on businesswire.com: http://www.businesswire.com/news/home/20151205005029/en/
Copyright Business Wire 2015