NEW YORK--(BUSINESS WIRE)--
Pfizer today announced that the Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a
positive opinion for LORVIQUA® (lorlatinib, approved in the
U.S., Canada, and Japan under the brand name LORBRENA®), an
anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI). The
CHMP has adopted a positive opinion recommending conditional marketing
authorization for LORVIQUA as monotherapy for the treatment of adult
patients with ALK-positive advanced non-small cell lung cancer (NSCLC)
whose disease has progressed after alectinib or ceritinib as the first
ALK TKI therapy, or crizotinib and at least one other ALK TKI.
Conversion to normal approval will be contingent on provisions of
comprehensive data confirming that the benefit-risk balance is positive.
The CHMP’s opinion will now be reviewed by the European Commission (EC),
with a decision expected in the coming months.
“Addressing drug resistance and relapse remains a challenge in the
treatment of ALK-positive non-small cell lung cancer,” said Chris
Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global
Product Development. “This CHMP opinion represents a step forward in
bringing LORVIQUA to patients in Europe living with advanced
ALK-positive non-small cell lung cancer who have limited treatment
options.”
The Marketing Authorization Application (MAA) for LORVIQUA was based on
results from a non-randomized, dose-ranging and activity-estimating,
multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating
LORVIQUA for the treatment of patients with ALK-positive advanced NSCLC,
who were previously treated with one or more ALK TKIs. A total of 229
patients with ALK-positive metastatic NSCLC were enrolled across various
subgroups based on prior treatment.
About LORVIQUA
®
(lorlatinib)
LORVIQUA is a TKI that has been shown to be highly active in preclinical
lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA
was specifically developed to inhibit tumor mutations that drive
resistance to other ALK inhibitors and to penetrate the blood brain
barrier.
LORVIQUA is approved in the U.S. under the brand name LORBRENA®
for the treatment of patients with anaplastic lymphoma kinase
(ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose
disease has progressed on crizotinib and at least one other ALK
inhibitor for metastatic disease, or whose disease has progressed on
alectinib or ceritinib as the first ALK inhibitor therapy for metastatic
disease. This indication is approved under accelerated approval based on
tumor response rate and duration of response. Continued approval for
this indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial. It is also approved in Japan
and Canada.
LORBRENA® (lorlatinib) IMPORTANT SAFETY INFORMATION FROM THE U.S.
PRESCRIBING INFORMATION
Contraindications: LORBRENA is contraindicated in patients taking
strong CYP3A inducers, due to the potential for serious hepatotoxicity.
Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A
Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy
subjects receiving a single dose of LORBRENA with multiple daily doses
of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations
occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in
8% of subjects. Discontinue strong CYP3A inducers for 3 plasma
half-lives of the strong CYP3A inducer prior to initiating LORBRENA.
Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If
concomitant use of moderate CYP3A inducers cannot be avoided, monitor
AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least
3 times during the first week after initiating LORBRENA. Depending upon
the relative importance of each drug, discontinue LORBRENA or the CYP3A
inducer for persistent Grade 2 or higher hepatotoxicity.
Central Nervous System (CNS) Effects: A broad spectrum of CNS
effects can occur. These include seizures, hallucinations, and changes
in cognitive function, mood (including suicidal ideation), speech,
mental status, and sleep. Withhold and resume at the same or reduced
dose or permanently discontinue based on severity.
Hyperlipidemia: Increases in serum cholesterol and triglycerides
can occur. Grade 3 or 4 elevations in total cholesterol occurred in 17%
and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332
patients who received LORBRENA. Eighty percent of patients required
initiation of lipid-lowering medications, with a median time to onset of
start of such medications of 21 days. Initiate or increase the dose of
lipid-lowering agents in patients with hyperlipidemia. Monitor serum
cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months
after initiating LORBRENA, and periodically thereafter. Withhold and
resume at same dose for the first occurrence; resume at same or reduced
dose of LORBRENA for recurrence based on severity.
Atrioventricular (AV) Block: PR interval prolongation and AV
block can occur. In 295 patients who received LORBRENA at a dose of 100
mg orally once daily and who had a baseline electrocardiography (ECG),
1% experienced AV block and 0.3% experienced Grade 3 AV block and
underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA
and periodically thereafter. Withhold and resume at reduced or same dose
in patients who undergo pacemaker placement. Permanently discontinue for
recurrence in patients without a pacemaker.
Interstitial Lung Disease (ILD)/Pneumonitis: Severe or
life-threatening pulmonary adverse reactions consistent with
ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of patients,
including Grade 3 or 4 ILD/pneumonitis in 1.2% of patients. Promptly
investigate for ILD/pneumonitis in any patient who presents with
worsening of respiratory symptoms indicative of ILD/pneumonitis.
Immediately withhold LORBRENA in patients with suspected
ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related
ILD/pneumonitis of any severity.
Embryo-fetal Toxicity: LORBRENA can cause fetal harm.Advise
pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to use an effective non-hormonal method of
contraception, since LORBRENA can render hormonal contraceptives
ineffective, during treatment with LORBRENA and for at least 6 months
after the final dose. Advise males with female partners of reproductive
potential to use effective contraception during treatment with LORBRENA
and for 3 months after the final dose.
Adverse Reactions: Serious adverse reactions occurred in 32% of
the 295 patients; the most frequently reported serious adverse reactions
were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status
changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions
occurred in 2.7% of patients and included pneumonia (0.7%), myocardial
infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%),
peripheral artery occlusion (0.3%), and respiratory distress (0.3%). The
most common (≥20%) adverse reactions were edema, peripheral neuropathy,
cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood
effects, and diarrhea; the most common (≥20%) laboratory abnormalities
were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia,
increased AST, hypoalbuminemia, increased ALT, increased lipase, and
increased alkaline phosphatase.
Drug Interactions: LORBRENA is contraindicated in patients taking
strong CYP3A inducers. Avoid concomitant use with moderate CYP3A
inducers and strong CYP3A inhibitors. If concomitant use of moderate
CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as
recommended. If concomitant use with a strong CYP3A inhibitor cannot be
avoided, reduce the LORBRENA dose as recommended. Concomitant use of
LORBRENA decreases the concentration of CYP3A substrates.
Lactation: Because of the potential for serious adverse reactions
in breastfed infants, instruct women not to breastfeed during treatment
with LORBRENA and for 7 days after the final dose.
Hepatic Impairment: No dose adjustment is recommended for
patients with mild hepatic impairment. The recommended dose of LORBRENA
has not been established for patients with moderate or severe hepatic
impairment.
Renal Impairment: No dose adjustment is recommended for patients
with mild or moderate renal impairment. The recommended dose of LORBRENA
has not been established for patients with severe renal impairment.
Please see full prescribing information for LORBRENA in the U.S. here.
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the most common cancer worldwide, with more than two
million new cases diagnosed globally in 2018.1 About 85
percent of all lung cancers are identified as non-small cell, and
approximately 75 percent of these are metastatic, or advanced, at
diagnosis.2
ALK gene rearrangement is a genetic alteration that drives the
development of lung cancer in some patients.3,4 Epidemiology
studies suggest that approximately three to five percent of NSCLC tumors
are ALK-positive.5
About Pfizer in Lung Cancer
Pfizer Oncology is committed to addressing the unmet needs of patients
with lung cancer, the leading cause of cancer-related deaths worldwide
and a particularly difficult-to-treat disease. Pfizer strives to address
the diverse and evolving needs of patients with non-small cell lung
cancer (NSCLC) by developing efficacious and tolerable therapies,
including biomarker-driven therapies and immuno-oncology (IO) agents and
combinations. By combining leading scientific insights with a
patient-centric approach, Pfizer is continually advancing its work to
match the right patient with the right medicine at the right time.
Through our growing research pipeline and collaboration efforts, we are
committed to delivering renewed hope to patients living with NSCLC.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we
believe we can make a meaningful difference on the lives of patients.
Today, Pfizer Oncology has an industry-leading portfolio of 18 approved
innovative cancer medicines and biosimilars across more than 20
indications, including breast, prostate, kidney, lung and hematology.
Pfizer Oncology is striving to change the trajectory of cancer.
Pfizer Inc: Working together for a healthier world
®
At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world's
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DISCLOSURE NOTICE: The information contained in this release is as of
March 1, 2019. 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 about
LORVIQUA/LORBRENA (lorlatinib), a tyrosine kinase inhibitor, including a
potential indication in the EU and LORVIQUA/LORBRENA’s potential
benefits, that involve substantial risks and uncertainties that could
cause actual results to differ materially from those expressed or
implied by such statements. Risks and uncertainties include, among other
things, uncertainties regarding the commercial success of
LORVIQUA/LORBRENA; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical trials,
regulatory submission dates, regulatory approval dates and/or launch
dates, as well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations and assessments by
regulatory authorities; whether regulatory authorities will be satisfied
with the design of and results from our clinical studies; whether and
when applications for LORVIQUA/LORBRENA may be filed in any other
jurisdictions; whether and when the European Commission may approve the
pending application for LORVIQUA in the EU and whether and when any such
other applications for LORVIQUA/LORBRENA that may be pending or filed
may be approved by regulatory authorities, which will depend on myriad
factors, including making a determination as to whether the product’s
benefits outweigh its known risks and determination of the product’s
efficacy and, if approved, whether LORVIQUA/LORBRENA will be
commercially successful; decisions by regulatory authorities impacting
labeling, manufacturing processes, safety and/or other matters that
could affect the availability or commercial potential of
LORVIQUA/LORBRENA; and competitive developments.
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, 2018 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at
www.sec.gov
and
www.pfizer.com
.
1 World Health Organization. International Agency for
Research on Cancer. GLOBOCAN 2018: Lung fact sheet. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf.
Accessed September 2018.
2 Reade CA, Ganti AK. EGFR
targeted therapy in non-small cell lung cancer: potential role of
cetuximab. Biologics. 2009;3:215–224.
3 Chiarle
R, Voena C, Ambrogio C, et al. The anaplastic lymphoma kinase in the
pathogenesis of cancer. Nat Rev Cancer. 2008;8(1):11-23.
4
Guérin A, Sasane M, Zhang J, et al. ALK rearrangement testing and
treatment patterns for patients with ALK-positive non-small cell lung
cancer. Cancer Epidemiol. 2015;39(3):307-12.
5
Garber K. ALK, lung cancer, and personalized therapy: portent of the
future? J Natl Cancer Inst. 2010;102:672-675.
View source version on businesswire.com:
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Pfizer Media:
March 1, 2019 Jessica Smith (U.S.)
(212) 733-6213
Jessica.M.Smith@pfizer.com
Lisa
O’Neill (EU)
(44) 7929 339 560
Lisa.O'Neill@pfizer.com
Pfizer
Investors:
Ryan Crowe
(212) 733-8160
Ryan.Crowe@pfizer.com
Source: Pfizer