Pfizer Inc. : Pfizer's Crizotinib Receives Positive Opinion For Conditional Marketing Authorization From The Committee For Medicinal Products For Human Use For The Treatment Of Adults With Previously Treated ALK-Positive Advanced Non-Small Cell Lung Cancer In The EU
07/20/2012| 08:35am US/Eastern
Pfizer announced today that the Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a
positive opinion recommending that crizotinib be granted conditional
marketing authorization in the European Union (EU), for the treatment of
adults with previously treated anaplastic lymphoma kinase (ALK)-positive
advanced non-small cell lung cancer (NSCLC).
Similar to accelerated approvals in the United States, conditional
marketing authorizations in the EU are granted to medicinal products
with a positive benefit/risk assessment that address unmet medical needs
and whose availability would result in a significant public health
benefit. A conditional marketing authorization is renewable annually. If
crizotinib is granted conditional marketing authorization, Pfizer will
be required to submit data to the EMA from the recently completed
PROFILE 1007 study, which the company announced in June met its primary
endpoint in previously treated ALK-positive advanced NSCLC patients.
Following review of the 1007 results by CHMP, the European Commission
would then consider converting the conditional marketing authorization
to a normal marketing authorization.
"The CHMP's positive opinion brings us a step closer to potentially
offering a new personalized treatment to patients with advanced NSCLC
across Europe," said Mace Rothenberg, MD, senior vice president of the
clinical development and medical affairs for Pfizer's Oncology Business
Unit. "This achievement is made possible by our commitment to using
knowledge of the underlying genetic drivers of diseases to identify
patients most likely to benefit from treatment and to focus our clinical
development program on those patients."
The CHMP's positive opinion will be reviewed by the European Commission,
which has the authority to approve medicines for the European Union.
Pfizer anticipates a decision from the Commission in the coming months.
Crizotinib is an oral, first-in-class, anaplastic lymphoma kinase (ALK)
inhibitor. By inhibiting the ALK fusion protein, crizotinib blocks
signaling in a number of cell pathways that are believed to be critical
for the growth and survival of tumor cells, which may lead to growth
inhibition or regression of tumors.1,2
Crizotinib is an investigational agent and has not been approved in the
European Union. Crizotinib was first approved as XALKORI® in the U.S. in
August 2011 for the treatment of locally advanced or metastatic NSCLC
that is ALK-positive as detected by a Food and Drug Administration
(FDA)-approved test. This indication is based on response rate. There
are no data available demonstrating improvements in patient-reported
outcomes or survival with XALKORI. XALKORI also has received approval in
a number of other countries, including Switzerland, Canada, South Korea
and Japan. Additional applications are under regulatory review in
several countries worldwide.
Important XALKORI® (crizotinib) U.S. Safety Information3
Drug-induced hepatotoxicity with fatal outcome has occurred.
Transaminase elevations generally occurred within the first 2 months of
treatment. Monitor with liver function tests including Alanine
Aminotransferase Test (ALT) and total bilirubin once a month and as
clinically indicated, with more frequent repeat testing for increased
liver transaminases, alkaline phosphatase, or total bilirubin in
patients who develop transaminase elevations. Temporarily suspend, dose
reduce, or permanently discontinue XALKORI as indicated.
XALKORI has been associated with severe, life-threatening, or fatal
treatment-related pneumonitis in clinical trials with a frequency of 4
in 255 (1.6%) patients. All of these cases occurred within 2 months
after the initiation of treatment. Monitor patients for pulmonary
symptoms indicative of pneumonitis. Exclude other causes and permanently
discontinue XALKORI in patients with treatment-related pneumonitis. QTc
prolongation has been observed. Avoid use of XALKORI in patients with
congenital long QT syndrome. Consider periodic monitoring with
electrocardiograms (ECGs) and electrolytes in patients with congestive
heart failure, bradyarrhythmias, electrolyte abnormalities, or who are
taking medications that are known to prolong the QT interval.
Permanently discontinue XALKORI for grade 4 QTc prolongation. XALKORI
should be withheld for grade 3 QTc prolongation until recovery to ?
grade 1. Permanently discontinue XALKORI if grade 3 QTc prolongation
Detection of ALK-positive NSCLC using an FDA-approved test, indicated
for this use, is necessary for selection of patients for treatment with
XALKORI can cause fetal harm when administered to a pregnant woman based
on its mechanism of action. Women of childbearing potential should be
advised to avoid becoming pregnant while receiving XALKORI. If the
patient or their partner becomes pregnant while taking this drug,
apprise the patient of the potential hazard to the fetus.
Among the 397 patients for whom information on deaths and serious
adverse reactions is available, deaths within 28 days of the last dose
of study drug occurred in 45 patients. Ten (2.5%) patients died within
28 days of their first dose of study drug. Causes of death included
disease progression (32 patients), respiratory events (9), and other (4).
Safety of XALKORI was evaluated in 255 patients with locally advanced or
metastatic ALK-positive NSCLC in 2 single-arm clinical trials (Studies A
and B). The most common adverse reactions (?25%) across both studies
were vision disorder, nausea, diarrhea, vomiting, edema, and
constipation. Grade 3-4 adverse reactions in ?4% of patients in both
studies included ALT increased and neutropenia.
Vision disorders including visual impairment, photopsia, vision blurred,
vitreous floaters, photophobia, and diplopia were reported in 159 (62%)
patients in clinical trials. Consider ophthalmological evaluation,
particularly if patients experience photopsia or experience new or
increased vitreous floaters. Severe or worsening vitreous floaters
and/or photopsia could also be signs of a retinal hole or pending
retinal detachment. Advise patients to exercise caution when driving or
operating machinery due to the risk of developing a vision disorder.
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and
development of innovative treatment options to improve the outlook for
cancer patients worldwide. Our strong pipeline of biologics and small
molecules, one of the most robust in the industry, is studied with
precise focus on identifying and translating the best scientific
breakthroughs into clinical application for patients across a wide range
of cancers. By working collaboratively with academic institutions,
individual researchers, cooperative research groups, governments, and
licensing partners, Pfizer Oncology strives to cure or control cancer
with breakthrough medicines, to deliver the right drug for each patient
at the right time. For more information please visit www.Pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of
July 20, 2012. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new information or
future events or developments.
This release contains forward-looking information that involves
substantial risks and uncertainties about an oncology product candidate,
crizotinib, including its potential benefits, that is under review by
regulatory authorities in the EU and various other jurisdictions. Such
risks and uncertainties include, among other things, the uncertainties
inherent in research and development; whether and when the European
Commission and regulatory authorities in various other jurisdictions
will approve drug applications that have been or may be filed for
crizotinib as well as their decisions regarding labeling and other
matters that could affect its availability or commercial potential; and
A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended December
31, 2011 and in its reports on Form 10-Q and Form 8-K.
1 Chiarle R, Voena C, Ambrogio C et al. The anaplastic
lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer.
2 Zou HY, Li Q, Lee JH, et al. An orally available
small-molecule inhibitor of c-MET, PF-2341066, exhibits cytoreductive
antitumor efficacy through antiproliferative and antiangiogenic
mechanisms. Cancer Res. 2007;67:4408-4417.
3 XALKORI [Package Insert]. New York, NY: Pfizer, Inc. 2011.
Jenifer Antonacci, (+1) 610-427-0369
Ojanen, (+44) 7557-202-394
Davis, (+1) 212-733-0717
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