Pfizer Inc. (NYSE: PFE) today announced that the European
Commission (EC) granted conditional marketing authorization for
LORVIQUA® (lorlatinib, available in the U.S., Canada and Japan
under the brand name LORBRENA®), as a monotherapy for the treatment
of adult patients with anaplastic lymphoma kinase (ALK)-positive
advanced non-small cell lung cancer (NSCLC) whose disease has
progressed after alectinib or ceritinib as the first ALK tyrosine
kinase inhibitor (TKI) therapy, or crizotinib and at least one
other ALK TKI. LORVIQUA is a third-generation ALK TKI that was
specifically developed to penetrate the blood brain barrier, in the
presence or absence of resistance mutations.
“Pfizer has worked to pioneer biomarker-driven medicine for
patients with ALK-positive non-small cell lung cancer and we
continue to advance patient care with the approval of LORVIQUA,”
said Andreas Penk, M.D., regional president, Oncology International
Developed Markets at Pfizer. “We are proud that LORVIQUA is our
second lung cancer medication approved in Europe within two months
and our third biomarker-driven medicine for lung cancer. We look
forward to making LORVIQUA available for European patients with
ALK-positive non-small cell lung cancer who have progressed on
prior therapy with a second generation ALK medicine.”
The conditional marketing authorization 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 139 patients with ALK-positive metastatic NSCLC after
treatment with at least one second-generation ALK TKI, such as
alectinib, brigatinib or ceritinib, were enrolled in the Phase 2
portion of the study. Among these patients, the overall response
rate (ORR) for those who have been treated with one prior ALK TKI
(N=28) was 42.9% (95% CI: 24.5, 62.8) and 39.6% (95% CI: 30.5,
49.4) for those with two or more prior ALK TKI treatments (N=111).
In the trial, 67% of patients had a history of brain
metastases.
“Over the last decade, our understanding of ALK-positive
non-small cell lung cancer has advanced dramatically, leading to
multiple medications for patients. However, the common challenges
associated with treating the disease, including resistance and
brain metastases have created an urgent need for additional
treatment options,” said Enriqueta Felip, M.D., Ph.D., Vall
d’Hebron University Hospital, Vall d’Hebron Institute of Oncology
in Spain. “The LORVIQUA approval marks an exciting time in lung
cancer innovation and I look forward to using this next-generation
ALK inhibitor to treat my patients.”
Among 295 ALK-positive or ROS1-positive metastatic NSCLC
patients who received LORVIQUA 100 mg once daily in study B7461001,
the most common (≥ 20%) adverse reactions were hypercholesterolemia
(84.4%), hypertriglyceridemia (67.1%), edema (54.6%), peripheral
neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%),
weight increased (26.4%), arthralgia (24.7%), mood effects (22.7%)
and diarrhea (22.7%).
Conditional approval is granted to a medicinal product that
fulfils an unmet medical need, where the benefit-risk balance is
positive and the benefit of the product’s immediate availability
outweighs the risk of less comprehensive data than normally
required.1 Under the provisions of the conditional approval, Pfizer
will provide additional data from the post-marketing studies,
including the Phase 3 CROWN study of LORVIQUA versus crizotinib in
the first-line treatment of patients with ALK-positive NSCLC, which
is currently ongoing.
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 EU
as monotherapy for the treatment of adult patients with
ALK-positive advanced NSCLC whose disease has progressed after:
- alectinib or ceritinib as the first ALK
TKI therapy; or
- crizotinib and at least one other ALK
TKI.
LORVIQUA is also approved:
- Under the brand name LORBRENA® in Japan
for the treatment of ALK fusion gene-positive unresectable advanced
and/or recurrent NSCLC with resistance or intolerance to ALK
tyrosine kinase inhibitor(s).
- Under the brand name LORBRENA® in
Canada, where it is conditionally approved as monotherapy for the
treatment of adult patients with ALK-positive metastatic NSCLC who
have progressed on: crizotinib and at least one other ALK
inhibitor, or patients who have progressed on ceritinib or
alectinib.
- Under the brand name LORBRENA® in the
U.S. for the treatment of patients with ALK-positive metastatic
NSCLC whose disease has progressed on:
- crizotinib and at least one other ALK
inhibitor for metastatic disease; or
- alectinib as the first ALK inhibitor
therapy for metastatic disease; or
- ceritinib as the first ALK inhibitor
therapy for metastatic disease.
The U.S. 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.
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
Lung cancer is the most common cancer worldwide, with more than
two million new cases diagnosed globally in 2018.2 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.3
ALK gene rearrangement is a genetic alteration that drives the
development of lung cancer in some patients.4,5 Epidemiology
studies suggest that approximately three to five percent of NSCLC
tumors are ALK-positive.6
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 best-known consumer health care
products. Every day, Pfizer colleagues work across developed and
emerging markets to advance wellness, prevention, treatments and
cures that challenge the most feared diseases of our time.
Consistent with our responsibility as one of the world's premier
innovative biopharmaceutical companies, we collaborate with health
care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world.
For more than 150 years, we have worked to make a difference for
all who rely on us. We routinely post information that may be
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addition, to learn more, please visit us on www.pfizer.com and
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DISCLOSURE NOTICE:
The information contained in this release is as of May 7, 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
(lorlatinib), a kinase inhibitor, and an approval by the European
Commission, including the 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,
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 may be filed in other
jurisdictions; whether and when any such other applications for
LORVIQUA 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 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; 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 European Medicines Agency. Conditional
Marketing Authorisation.
https://www.ema.europa.eu/en/human-regulatory/marketing-authorisation/conditional-marketing-authorisation.
Accessed March 2019.
2 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.
3 Reade CA, Ganti AK. EGFR targeted
therapy in non-small cell lung cancer: potential role of cetuximab.
Biologics. 2009;3:215–224.
4 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.
5 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.
6 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: https://www.businesswire.com/news/home/20190507005509/en/
Pfizer Media:Jessica Smith (U.S.)(212)
733-6213Jessica.M.Smith@pfizer.com
Lisa O’Neill (EU)(44) 7929 339 560Lisa.O'Neill@pfizer.com
Pfizer Investor:Ryan Crowe(212)
733-8160Ryan.Crowe@pfizer.com
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