INCYTE : Reaches Agreement with the FDA on a Special Protocol Assessment for the Phase III Clinical Trial of INCB18424 in Polycythemia Vera
09/13/2010| 07:10am US/Eastern
Incyte Corporation (Nasdaq:INCY) announced today that it has
reached agreement with the U.S. Food and Drug Administration (FDA)
regarding a Special Protocol Assessment (SPA) for the design of a
pivotal Phase III trial for its JAK1 and JAK2 inhibitor, INCB18424 in
patients with polycythemia vera (PV), a blood cancer that belongs to a
group of diseases known as myeloproliferative neoplasms (MPNs). Two
Phase III trials of INCB18424 in myelofibrosis, also an MPN, COMFORT-I
and COMFORT-II, are already fully enrolled and are expected to be
completed later this year.
RESPONSE (Randomized, open label, multicenter phase III study of Efficacy
and Safety in POlycythemia vera subjects who are resistant
to or intolerant of hydroxyurea: JAK iNhibitor INC424 tablets verSus
bEst available care) is a global study conducted by Incyte in the
US and Novartis in rest of world and is expected to enroll approximately
300 patients with PV who are resistant to or intolerant of hydroxyurea
(HU). RESPONSE will compare the efficacy and safety of INCB18424 to the
physician's choice of best available therapy. Patient enrollment in the
US is expected to begin in October (www.responsetrial.com).
?Securing the SPA for INCB18424 in PV establishes the requirements we
must meet to obtain approval in this second indication and supports our
objective to expand beyond myelofibrosis,? stated Paul A. Friedman,
M.D., Incyte's President and CEO. ?The encouraging results from the
ongoing Phase II PV trial, combined with the data we anticipate
achieving from RESPONSE, have the potential to clearly establish the
long-term safety and efficacy of INCB18424 and optimally position the
compound for use in these underserved patients.?
Srdan Verstovsek, M.D., Ph.D., Associate Professor, Leukemia Department,
Myeloproliferative Disorders Program Leader, University of Texas M.D.
Anderson Cancer Center, and the US principal investigator for RESPONSE,
stated, ?Patients with advanced PV represent a particularly high-risk
group with few therapeutic options for long-term care. These patients
would benefit from new chronic therapies that safely and effectively
address the aberrant hematological measures, enlarged spleens and
significant disease-related symptoms that so negatively impact their
lives. In previous trials, INCB18424 has been well tolerated in patients
with advanced PV, and much sicker patients with myelofibrosis for as
long as 30 months. In the Phase II trial involving 34 PV patients who
were HU resistant or HU intolerant, INCB18424 provided rapid and durable
activity in these patients. We look forward to evaluating INCB18424 in
this Phase III trial designed in agreement with FDA.?
RESPONSE is a global, randomized, open-label, multi-center Phase III
trial that will compare the efficacy and safety of the oral JAK1 and
JAK2 inhibitor INCB18424 to best available therapy in approximately 300
patients with PV. To be eligible for the study, patients must be
resistant to or intolerant of HU, require phlebotomy based on inadequate
hematocrit control at least once every three months, possess an elevated
white blood cell count and/or platelet count and exhibit a palpated
spleen length of 5 cm or greater.
Primary efficacy endpoint
The proportion of patients treated with INCB18424 versus best available
therapy achieving a response at week 32, with response defined as having
achieved both of the following:
the absence of phlebotomy and
a ?35% reduction in spleen volume as assessed by imaging
Key secondary efficacy endpoints
Proportion of patients treated with INCB18424 versus best available
therapy who both achieve the week 32 primary response endpoint and
maintain response for 48 weeks from the time that response was
Proportion of patients treated with INCB18424 versus best available
therapy achieving complete hematologic remission at week 32
Duration of trial
The randomized, controlled period of the trial is 32 weeks. Data are
scheduled to be analyzed when the last patient remaining in the study
has completed week 80 (i.e. 48 weeks following the primary endpoint at
week 32) to enable the assessment of response durability. Patients
receiving benefit from INCB18424 at week 80 will be eligible to continue
to receive INCB18424 in a separate open-label extension study.
Best available therapy
Therapy will be selected by the investigator on a patient-by-patient
basis among the following six options: interferon/pegylated interferon,
pipobroman, anagrelide, immunomodulators (imids such as lenalidomide and
thalidomide), HU (at a tolerated dose if, in the opinion of the
investigator, the patient is likely to receive benefit), and observation
only (i.e. absence of treatment apart from aspirin and phlebotomy when
the subject is eligible). The dose and administration schedule of
initial best available therapy may be changed at any time, however the
initial therapy may only be changed if specific treatment
discontinuation or disease progression criteria are met.
Cross-over from best available therapy to INCB18424
Patients randomized to best available therapy, who fail to meet the
primary endpoint at week 32 or whose response ends subsequent to week
32, may be eligible to cross over to receive INCB18424.
Current Approach to Treating PV
The current therapeutic approach in PV focuses on lowering the risk for
thrombotic events without exposing patients to increased risk of
leukemic transformation1. While phlebotomy and low dose
aspirin are accepted as the standard of care for initial therapy,
cytoreductive therapy is recommended to aid in the control of
erythrocytosis in the presence of poor tolerance to phlebotomy,
symptomatic or progressive splenomegaly, or evidence of high thrombotic
risk2. Though not FDA approved for use in PV, HU is the most
frequently used myelosuppressive agent for initial cytoreductive therapy2.
HU treatment is associated with cytopenias and often unsatisfactory
hematological control over time, aphthous and leg ulcers, multiple other
toxicities, and risk of leukemia estimated at up to 10% at the 13th year3,4.
Therapeutic options beyond HU are limited, and as a consequence, it is
estimated that up to 20% of patients may continue on HU even though
response is less than satisfactory4.
About Special Protocol Assessment
The SPA is a process that allows for official FDA evaluation of the
clinical protocols of a Phase III clinical trial intended to form the
primary basis for an efficacy claim and provides trial sponsors with a
written agreement that the design and analysis of the trial are adequate
to support a New Drug Application (NDA) if the trial is performed
according to the SPA. Final marketing approval depends on the results of
efficacy, the adverse event profile and on an evaluation of the
benefit/risk of treatment demonstrated in the Phase III trial. The SPA
agreement may only be changed through a written agreement between the
sponsor and the FDA, or if the FDA becomes aware of a substantial
scientific issue essential to product efficacy or safety. For more
information on Special Protocol Assessment, please visit the FDA web
site at www.FDA.gov.
About PV and INCB18424
PV is a characterized by the overproduction of red blood cells which
increases blood viscosity and leads to elevated thromboembolic risk.
Increased levels of white blood cells and platelets are also common. In
advanced disease, patients frequently exhibit spleen enlargement and
debilitating symptoms including pruritus, night sweats, fatigue, and
muscle and bone pain. In the Phase II trial, as presented at the
American Society of Hematology Annual Meeting, December 2009, clinical
benefits associated with INCB18424 treatment in the 34 PV patients
enrolled in the study included hematocrit control without the need for
phlebotomy, normalization of white blood cell and platelet counts, and
rapid and durable reductions in enlarged spleens and symptoms,
particularly pruritus. INCB18424 was generally well tolerated in these
patients, and the most common adverse events observed involved low blood
cell counts which, in the majority of patients, were reversed by dose
About the Incyte Novartis Alliance
In November 2009, Incyte and Novartis announced a major collaboration
and license agreement for two hematology-oncology programs in which
Incyte retained exclusive rights to develop and commercialize INCB18424
in the US and Novartis received exclusive rights to develop and
commercialize INCB18424 for territories outside the US. Novartis also
received worldwide rights for Incyte's cMET Inhibitor, INCB28060.
Incyte Corporation is a Wilmington, Delaware-based drug discovery and
development company focused on developing proprietary small molecule
drugs for oncology and inflammation. Incyte's most advanced compound,
INCB18424, is in Phase III development for myelofibrosis. 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 with respect to
the anticipated completion of COMFORT-I and COMFORT-II in patients with
myelofibrosis, the expected number of patients and time to begin
enrollment of patients in RESPONSE, the anticipated data from RESPONSE
combined with the results from the ongoing Phase II PV trial having the
potential to establish the long-term safety and efficacy of INCB18424
within the segment of advanced PV patients and optimally positioning the
compound for use in these patients, and the anticipated schedule for
analysis of data from RESPONSE, 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 trials, the uncertainty associated with the regulatory approval
processes, uncertainty regarding the timing of commencement of RESPONSE,
the ability to enroll a sufficient number of patients for RESPONSE in a
timely manner or at all, unanticipated developments in the efficacy or
safety of INCB18424, 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 June 30, 2010.
Incyte disclaims any intent or obligation to update these
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you to consult these policy statements. Incyte has no control over third
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1. Finazzi G, Barbui T. (2008) Evidence and expertise in the management
of polycythemia vera and essential thrombocythemia. Leukemia.;
2. Finazzi G, Barbui T. (2007) How I treat patients with polycythemia
vera. Blood.;109:5104- 5111.
3. Tefferi A. (2003) Polycythemia vera: a comprehensive review and
clinical recommendations. Mayo Clin Proc.;78:174-94.
4. Najean Y, Rain JD. (1997) Treatment of polycythemia vera: The use of
hydroxyurea and pipobroman in 292 patients under the age of 65 years.
Pamela M. Murphy, 302/498-6944
President, Investor Relations/Corporate Communications
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