Incyte Corporation (Nasdaq: INCY) today announced that The New
England Journal of Medicine (NEJM) published results from the
pivotal Phase III RESPONSE clinical trial demonstrating that, compared
to standard therapy, Jakafi® (ruxolitinib) significantly
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 hydroxyurea1.
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 count2. PV may occur at any age but often
presents later in life, with a median age at diagnosis of 60 years2,3.
Approximately 100,000 patients in the U.S. are living with PV4.
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 utilized5,6.
Approximately one in four (~25,000) patients with PV are considered
uncontrolled7,8 because they had an inadequate response to or
had unacceptable side effects from hydroxyurea, the most commonly used
chemotherapeutic agent for the treatment of PV.
“A key challenge in treating patients with PV is the development of
resistance or intolerance to currently available therapies such as
hydroxyurea, which leaves us with no effective treatment options to
manage the disease,” said Dr. Alessandro M. Vannucchi, Department of
Hematology, University of Florence, Italy and lead study author. “This
study indicates that ruxolitinib may represent an important advance for
patients with uncontrolled PV.”
In the RESPONSE trial, a significantly greater proportion of patients
achieved the composite primary endpoint of hematocrit control without
use of phlebotomy and at least a 35% spleen volume reduction when
treated with ruxolitinib compared to standard therapy (21% compared to
1%, respectively; p<0.001) as measured at week 32, and 91% of these
patients treated with ruxolitinib maintained their response at week 481.
Assessing the components of the composite primary endpoint separately,
60% of patients randomized to ruxolitinib achieved hematocrit control
without use of phlebotomy in comparison with 20% of patients randomized
to standard therapy; 38% of patients randomized to ruxolitinib achieved
at least a 35% spleen volume reduction in comparison with 1% of patients
randomized to standard therapy1. 77% of patients
randomized to ruxolitinib achieved one or both components of the
composite primary endpoint, in comparison with 20% of patients
randomized to standard therapy1. Additionally, 84.5% of
patients randomized to ruxolitinib were still receiving treatment at a
median follow-up of 81 weeks1.
A greater proportion of patients on the ruxolitinib treatment arm
achieved complete hematologic remission, a key secondary endpoint, when
compared to the standard therapy arm (24% compared to 9%, respectively;
p=0.003)1. Complete hematologic remission was defined9
as achieving hematocrit control without the use of phlebotomy, platelet
count ≤400 x 109/L and white blood cell count ≤10 × 109/L,
which are all important markers of disease control in PV.
“The publication of the data from our pivotal RESPONSE Phase III study
demonstrates the importance of Jakafi as the first FDA-approved
treatment for patients with uncontrolled polycythemia vera,” stated Rich
Levy, M.D., Incyte’s EVP, Chief Drug Development and Medical Officer.
“These data, together with those seen with Jakafi therapy in
myelofibrosis, add further to our confidence in the potential
therapeutic value of JAK inhibition in the treatment of patients with
myeloproliferative neoplasms.”
Overall, non-hematologic adverse events (AEs) were consistent with those
previously seen in ruxolitinib studies in PV and myelofibrosis1,10,11.
Within the first 32 weeks of treatment, the most common non-hematologic
AEs in the ruxolitinib arm were headache (16.4%), diarrhea (14.5%) and
fatigue (14.5%), which were mainly Grade 1 or 21. During the
first 32 weeks, grade 3/4 anemia or thrombocytopenia occurred in 2% and
5% of ruxolitinib patients, respectively, vs 0% and 4% of standard
therapy patients1.
Study Design
RESPONSE is a global, randomized, open-label Phase III study conducted
at more than 90 sites. 222 patients with PV resistant to or intolerant
of hydroxyurea were randomized 1:1 to receive either ruxolitinib
(starting dose of 10 mg twice daily) or standard therapy (best available
therapy), which was defined as investigator-selected monotherapy or
observation only1. Ruxolitinib dose could be adjusted as
needed throughout the study1.
The primary endpoint of the study was the proportion of patients whose
hematocrit was controlled without phlebotomy eligibility from week 8
through 32 (with no more than one phlebotomy eligibility between
randomization and week 8) and whose spleen volume was reduced by 35% or
more from baseline as assessed by imaging at week 321.
Phlebotomy eligibility was defined as hematocrit (volume percentage of
red blood cells in whole blood) greater than 45% and that was ≥3
percentage points higher than baseline, or hematocrit greater than 48%,
whichever was lower. In addition, efficacy was further assessed using
two key secondary endpoints: durable primary response and complete
hematological remission1. Other endpoints included safety,
symptom improvement (as measured by the MPN-SAF 14-item total symptom
score) and quality of life1.
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 count2. 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 death12.
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 body13. These
symptoms commonly include fatigue, itching, night sweats, bone pain,
fever, and weight loss6.
Approximately 100,000 patients in the U.S. are living with PV4.
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 utilized5,6.
Approximately one in four patients with PV are considered uncontrolled7,8
because they have an inadequate response to or are intolerant of
hydroxyurea, the most commonly used chemotherapeutic agent for the
treatment of PV.
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.
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.
Please see the Full Prescribing Information available at www.jakafi.com,
which includes a more complete discussion of the risks associated with
Jakafi.
Forward-Looking Statements
Except for the historical information set forth herein, the matters set
forth in this press release, including without limitation statements
with respect to the potential efficacy, safety and therapeutic value of
Jakafi® (ruxolitinib) in uncontrolled polycythemia vera, and
the potential therapeutic value of JAK inhibition in myeloproliferative
neoplasms, contain predictions and estimates and are 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 based on Incyte’s current expectations and subject to
risks and uncertainties that may cause actual results to differ
materially, including unanticipated developments in and risks related to
the efficacy or safety of Jakafi, the results of further research and
development, other market or economic factors, competitive and
technological advances, 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 September 30,
2014. Incyte disclaims any intent or obligation to update these
forward-looking statements.
References
1 Vannucchi A, et al. Ruxolitinib versus Standard Therapy for
the Treatment of Polycythemia Vera. The New England Journal of Medicine.
2015 372;5.
2 Leukemia & Lymphoma Society. Polycythemia Vera Facts 2012.
Available at: https://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/polycythemiavera.pdf.
3 Tefferi A, Rumi E, Finazzi G, et al. Leukemia.
2013;27:1874-81.
4 Data on file. Incyte Corporation
5 Vannucchi AM. Blood 2014; 124(22):3212-20.
6 Passamonti F. Blood 2012; 120(2):275-84.
7 Barosi G, Birgegard G, Finazzi G, et al. Br J Haematol.
2010; 149:961-3.
8 Alvarez-Larrán A, Pereira A, Cervantes F, et al. Blood.
2012; 119:1363-9
9 Modified 2009 European LeukemiaNet (ELN) criteria.
10 Vannucchi, A, et al. Long-Term Outcomes from a Phase 3
Study Comparing Ruxolitinib with Best Available Therapy (BAT) for the
Treatment of Myelofibrosis (MF): A 3 Year Update of Comfort II. Abstract
# S1111.18th Congress of European Hematology Association (EHA), 2013.
Stockholm, Sweden.
11 Verstovsek S, Ruben M, Gotlib J, et al. Long-Term Outcome
of Ruxolitinib Therapy in Patients with Myelofibrosis: 3-Year Update
from COMFORT-I. Abstract #396. 55th American Society of Hematology (ASH)
Annual Meeting and Exposition, 2013. New Orleans, LA.
12 Marchioli R, et al. N Engl J Med. 2013;368:22-33.
13 National Institutes of Health http://www.nhlbi.nih.gov/health/health-topics/topics/poly/signs.
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