MYLOTARG (gemtuzumab ozogamicin) Granted a
Positive Opinion for the Treatment of Previously Untreated, De
Novo, CD33-positive Acute Myeloid Leukemia in Combination with
Chemotherapy
BOSULIF (bosutinib) Granted a Positive Opinion
for the Treatment of Newly Diagnosed Ph+ Chronic Myelogenous
Leukemia
Pfizer Inc. (NYSE:PFE) today announced that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMA) has adopted positive opinions recommending that two
Pfizer hematology medicines be granted marketing authorizations in
the European Union (EU). MYLOTARG™ (gemtuzumab ozogamicin) in
combination with daunorubicin and cytarabine has been granted a
positive opinion for the treatment of patients age 15 years and
above with previously untreated, de novo, CD33-positive acute
myeloid leukemia (AML), except acute promyelocytic leukemia (APL).
BOSULIF® (bosutinib) has been granted a positive opinion for the
treatment of adults with newly diagnosed chronic phase Philadelphia
chromosome-positive chronic myelogenous leukemia (Ph+ CML). The
CHMP’s opinions for both medicines will now be reviewed separately
by the European Commission (EC).
“There is an urgent need to improve outcomes for leukemia
patients in Europe,” said Mace Rothenberg, M.D., chief development
officer, Oncology, Pfizer Global Product Development. “If approved,
the addition of MYLOTARG to standard chemotherapy will provide an
important new treatment option for patients with acute myeloid
leukemia who would typically be treated with chemotherapy alone.
Additionally, the potential expansion of the approved use of
BOSULIF to include first-line therapy expands the treatment options
for adult patients with newly diagnosed chronic myelogenous
leukemia.”
The Marketing Authorization Application (MAA) for MYLOTARG was
based on data from an investigator-led, Phase 3, randomized,
open-label study (ALFA-0701) in previously untreated, de novo
patients.
BOSULIF currently has conditional marketing authorization in
Europe related to the initial marketing authorization. The Type II
Variation application for BOSULIF for adults with newly diagnosed
chronic phase Ph+ CML was based on results from BFORE
(Bosutinib trial in First line chrOnic
myelogenous leukemia tREatment), a randomized multicenter,
multinational, open-label, Phase 3, head-to-head study of BOSULIF
400 mg versus imatinib 400 mg, a current standard of care.
Pfizer and Avillion entered into an exclusive collaborative
development agreement in 2014 to conduct the BFORE trial. Under the
terms of the agreement, Avillion provided funding for the trial to
generate the clinical data used to support this application and
other potential regulatory filings for marketing authorization for
BOSULIF as first-line treatment for patients with chronic phase Ph+
CML. Pfizer retains all rights to commercialize BOSULIF
globally.
IMPORTANT MYLOTARG™ (gemtuzumab ozogamicin) SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
WARNING: Hepatotoxicity, including severe or fatal hepatic
veno-occlusive disease (VOD), also known as sinusoidal obstruction
syndrome (SOS), has been reported in association with the use of
MYLOTARG as a single agent, and as part of a combination
chemotherapy regimen. Monitor frequently for signs and symptoms of
VOD after treatment with MYLOTARG.
Hepatotoxicity, Including Veno-occlusive Liver Disease
(VOD): An increased risk of VOD was observed in patients with
moderate/severe hepatic impairment and patients who received
MYLOTARG either before or after HSCT. Assess ALT, AST, total
bilirubin, and alkaline phosphatase prior to each dose of MYLOTARG.
After treatment with MYLOTARG, monitor frequently for signs and
symptoms of VOD; these may include elevations in ALT, AST, and
total bilirubin, hepatomegaly, rapid weight gain, and ascites.
Monitoring only total bilirubin may not identify all patients at
risk of VOD. For patients who develop abnormal liver tests, more
frequent monitoring of liver tests and clinical signs and symptoms
of hepatotoxicity is recommended. For patients who proceed to HSCT,
monitor liver tests frequently during the post-HSCT period, as
appropriate. Manage signs or symptoms of hepatic toxicity by dose
interruption or discontinuation of MYLOTARG. In patients who
experience VOD, discontinue MYLOTARG and treat according to
standard medical practice.
Infusion-Related Reactions (Including Anaphylaxis):
Life-threatening or fatal infusion-related reactions can occur
during or within 24 hours following infusion of MYLOTARG. Signs and
symptoms of infusion-related reactions may include fever, chills,
hypotension, tachycardia, hypoxia, and respiratory failure.
Premedicate prior to MYLOTARG infusion. Monitor vital signs
frequently during infusion. Interrupt infusion immediately for
patients who develop evidence of infusion reaction, especially
dyspnea, bronchospasm, or hypotension. Monitor patients during and
for at least 1 hour after the end of the infusion or until signs
and symptoms completely resolve. Discontinue use of MYLOTARG in
patients who develop signs or symptoms of anaphylaxis, including
severe respiratory symptoms or clinically significant
hypotension.
Hemorrhage: MYLOTARG is myelosuppressive and can cause
fatal or life-threatening hemorrhage due to prolonged
thrombocytopenia. Assess blood counts prior to each dose of
MYLOTARG and monitor blood counts frequently after treatment with
MYLOTARG until resolution of cytopenias. Monitor patients for signs
and symptoms of bleeding during treatment with MYLOTARG. Manage
severe bleeding, hemorrhage, or persistent thrombocytopenia using
dose delay or permanent discontinuation of MYLOTARG, and provide
supportive care per standard practice.
QT Interval Prolongation: QT interval prolongation has
been observed in patients treated with other drugs containing
calicheamicin. When administering MYLOTARG to patients who have a
history of or predisposition for QTc prolongation, who are taking
medicinal products that are known to prolong QT interval, and in
patients with electrolyte disturbances, obtain electrocardiograms
and electrolytes prior to the start of treatment and as needed
during administration.
Adverse Cytogenetics: In a subgroup analysis in
ALFA-0701, the addition of MYLOTARG to standard combination
chemotherapy did not improve event-free survival in the subgroup of
patients having adverse-risk cytogenetics. For patients being
treated with MYLOTARG in combination with daunorubicin and
cytarabine for newly diagnosed de novo AML, when cytogenetics
testing results become available consider whether the potential
benefit of continuing treatment with MYLOTARG outweighs the risks
for the individual patient.
Embryo-Fetal Toxicity: MYLOTARG can cause embryo-fetal
harm when administered to a pregnant woman. Advise patients of
reproductive potential to use effective contraception during and
for 3 and 6 months following treatment for males and females,
respectively. Apprise pregnant women of the potential risk to the
fetus. Advise women to contact their healthcare provider if they
become pregnant or if pregnancy is suspected during treatment with
MYLOTARG.
Adverse Reactions: The most common adverse reactions
(greater than 15%) were hemorrhage, infection, fever, nausea,
vomiting, constipation, headache, increased AST, increased ALT,
rash, and mucositis.
Contraindications: Hypersensitivity to MYLOTARG or any of
its components. Reactions have included anaphylaxis.
The full U.S. prescribing information, including BOXED WARNING,
for MYLOTARG can be found here.
IMPORTANT BOSULIF® (bosutinib) SAFETY INFORMATION FROM THE
U.S. PRESCRIBING INFORMATION
Contraindication: History of hypersensitivity to
BOSULIF. Reactions have included anaphylaxis. Anaphylactic shock
occurred in less than 0.2% of treated patients in single-agent
cancer studies with BOSULIF.
Gastrointestinal Toxicity: Diarrhea, nausea,
vomiting, and abdominal pain can occur. In the randomized clinical
trial of patients with newly diagnosed Ph+ CML, the median time to
onset for diarrhea (all grades) among patients in the BOSULIF
treatment group (n=268) was 3 days and the median duration per
event was 3 days. Among 546 patients in a single-arm study of
patients with CML who were resistant or intolerant to prior
therapy, median time to onset of diarrhea (all grades) was 2 days,
median duration was 2 days, and the median number of episodes per
patient was 3 (range 1-268). Monitor and manage patients using
standards of care, including antidiarrheals, antiemetics, and/or
fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as
necessary.
Myelosuppression: Thrombocytopenia, anemia, and
neutropenia can occur. Perform complete blood counts weekly for the
first month and monthly thereafter, or as clinically indicated.
Withhold, dose reduce, or discontinue BOSULIF as necessary.
Hepatic Toxicity: Elevations in serum transaminases
(alanine aminotransferase [ALT] and aspartate aminotransferase
[AST]) can occur. Perform hepatic enzyme tests at least monthly for
the first 3 months and as clinically indicated. In patients with
transaminase elevations, monitor liver enzymes more frequently. One
case consistent with drug-induced liver injury occurred without
alternative causes in a trial of BOSULIF in combination with
letrozole. Withhold, dose reduce, or discontinue BOSULIF as
necessary. In patients with mild, moderate, or severe hepatic
impairment, the recommended starting dose is 200 mg daily.
Renal Toxicity: An on-treatment decline in estimated
glomerular filtration rate has occurred in patients treated with
BOSULIF. Monitor renal function at baseline and during therapy,
with particular attention to patients with preexisting renal
impairment or risk factors for renal dysfunction. Consider dose
adjustment in patients with baseline and treatment-emergent renal
impairment.
Reduce the BOSULIF starting dose in patients with moderate
(creatinine clearance [CLcr] 30 to 50 mL/min) or severe (CLcr
less than 30 mL/min) renal impairment at baseline. For
patients who have declining renal function while on BOSULIF who
cannot tolerate the starting dose, follow dose adjustment
recommendations for toxicity.
Fluid Retention: Fluid retention can occur with
BOSULIF and may cause pericardial effusion, pleural effusion,
pulmonary edema, and/or peripheral edema. Among 546 patients in a
single-arm study of patients with Ph+ CML who were resistant or
intolerant to prior therapy, Grade 3/4 fluid retention was reported
in 26 patients (5%). Monitor and manage patients using standards of
care. Interrupt, dose reduce, or discontinue BOSULIF as
necessary.
Embryofetal Toxicity: BOSULIF can cause fetal harm
when administered to a pregnant woman. Women of childbearing
potential should be advised of the potential hazard to the fetus.
Advise females of reproductive potential to use effective
contraceptive measures to prevent pregnancy while being treated
with BOSULIF and for at least 1 month after the final dose.
Adverse Reactions: The most common adverse reactions
observed in greater than or equal to 20% of patients with newly
diagnosed CML were diarrhea, nausea, thrombocytopenia, rash,
increased ALT, abdominal pain, and increased AST. The most common
Grade 3/4 adverse reactions and laboratory abnormalities observed
in greater than 10% of newly diagnosed CML patients were
thrombocytopenia and increased ALT.
The most common adverse reactions observed in greater than or
equal to 20% of patients with CML who were resistant or intolerant
to prior therapy were diarrhea, nausea, abdominal pain, rash,
thrombocytopenia, vomiting, anemia, fatigue, pyrexia, cough,
headache, ALT, and edema. The most common Grade 3/4 adverse
reactions and laboratory abnormalities observed in greater than 10%
of patients who were resistant or intolerant to prior therapy were
thrombocytopenia, neutropenia, and anemia.
CYP3A Inhibitors and Inducers: Avoid concurrent use
with strong or moderate CYP3A inhibitors or strong CYP3A
inducers.
Proton Pump Inhibitors: Use short-acting antacids or
H2 blockers instead of PPIs to avoid a reduction in BOSULIF
exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing
by more than 2 hours.
Lactation: Because of the potential for serious
adverse reactions in a nursing child, breastfeeding is not
recommended during treatment with BOSULIF and for at least 1 month
after the last dose.
Please see full U.S. Prescribing Information for
BOSULIF here.
ABOUT ACUTE MYELOID LEUKEMIA (AML)
Acute myeloid leukemia is a rapidly progressing,
life-threatening blood and bone marrow cancer. 1 If left untreated,
patients with AML will die within months, if not weeks, of their
disease. AML is the most common type of acute leukemia in adults
and accounts for approximately 80% of all cases of acute leukemia.2
About 1/33,000-1/25,000 people are expected to be newly diagnosed
with AML in Europe annually.2
ABOUT CHRONIC MYELOGENOUS LEUKEMIA (CML)
Chronic myelogenous leukemia (CML) is a rare blood cancer, which
begins in the bone marrow, but often moves into the blood.3
Researchers estimate that by 2020, more than 412,000 people
worldwide will be diagnosed with leukemia (all types).4 Across
Europe, CML constitutes about 15% of all leukemia and occurs with
an incidence of about 1-1.5/100,000.5
About MYLOTARG™ (gemtuzumab ozogamicin)
MYLOTARG is an antibody-drug conjugate (ADC) composed of the
cytotoxic agent calicheamicin, attached to a monoclonal antibody
(mAB) targeting CD33, an antigen expressed on the surface of
myeloblasts in up to 90 percent of AML patients.6,7,8 When MYLOTARG
binds to the CD33 antigen on the cell surface it is absorbed into
the cell and calicheamicin is released causing cell death.7,8
MYLOTARG was approved by the U.S. Food and Drug Administration
in September 2017 for adults with newly diagnosed CD33-positive
AML, and adults and children 2 years and older with relapsed or
refractory CD33-positive AML. MYLOTARG was originally approved in
2000 at a higher dose under the FDA’s accelerated approval program
for use as a single agent in patients with CD33-positive AML who
had experienced their first relapse and were 60 years or older and
who were not considered candidates for other cytotoxic
chemotherapy. In 2010, Pfizer voluntarily withdrew MYLOTARG in the
U.S. after a confirmatory trial failed to show clinical benefit and
there was a higher rate of fatal toxicity compared to chemotherapy.
MYLOTARG has been available to individual patients through Pfizer’s
compassionate use programs.
In addition, MYLOTARG is commercially available in Japan where
it has been approved since 2005 for the treatment of patients with
relapsed or refractory CD33-positive AML who are not considered
candidates for other cytotoxic chemotherapy.
MYLOTARG originates from a collaboration between Pfizer and
Celltech, now UCB. Pfizer has sole responsibility for all
manufacturing, clinical development and commercialization
activities for this molecule.
Pfizer also collaborated with SFJ Pharmaceuticals Group on the
registrational program for MYLOTARG.
ABOUT BOSULIF® (bosutinib)
BOSULIF® (bosutinib) is an oral, once-daily, tyrosine
kinase inhibitor (TKI), which inhibits the Bcr-Abl kinase that
promotes CML; it is also an inhibitor of Src-family kinases. In the
U.S., BOSULIF (bosutinib) is indicated for the treatment of adult
patients with newly-diagnosed chronic phase Philadelphia
chromosome-positive chronic myelogenous leukemia (Ph+ CML).
Continued approval for this indication may be contingent upon
verification and confirmation of clinical benefit in an ongoing
long-term follow up trial. BOSULIF is also indicated in the U.S for
the treatment of adult patients with chronic, accelerated or blast
phase Ph+ CML with resistance or intolerance to prior therapy
(first approved in September 2012).
In Europe, BOSULIF was granted conditional marketing
authorization in March 2013 for the treatment of adult patients
with Ph+ CML previously treated with one or more TKIs and for whom
imatinib, nilotinib and dasatinib are not considered appropriate
treatment options.
About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments
that have a meaningful impact on people living with cancer. Our
growing pipeline of biologics, small molecules, and immunotherapies
is focused on identifying and translating the best scientific
breakthroughs into clinical application for patients across a
diverse array of solid tumors and hematologic cancers. Today, we
have 10 approved oncology medicines and 17 assets currently in
clinical development. By maximizing our internal scientific
resources and collaborating with other companies, government and
academic institutions, as well as non-profit and professional
organizations, we are bringing together the brightest and most
enterprising minds to take on the toughest cancers. Together we can
accelerate breakthrough treatments to patients around the world and
work to redefine life with cancer.
Pfizer Inc.: Working together for a healthier
worldTM
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
important to investors on our website at www.pfizer.com. In
addition, to learn more, please visit us on www.pfizer.com and
follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube
and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is
as of February 23, 2018. 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 Pfizer’s
oncology portfolio, MYLOTARG (gemtuzumab ozogamicin), an
antibody-drug conjugate, and BOSULIF (bosutinib), a tyrosine kinase
inhibitor, including potential indications in the EU and their
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
trial commencement and completion dates and regulatory submission
dates, as well as the possibility of unfavorable clinical trial
results, including unfavorable new clinical data and additional
analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations, and, even when we
view data as sufficient to support the safety and/or effectiveness
of a product candidate, regulatory authorities may not share our
views and may require additional data or may deny approval
altogether; whether regulatory authorities will be satisfied with
the design of and results from our clinical studies; whether and
when applications for MYLOTARG and BOSULIF may be filed in any
other jurisdictions; whether and when the European Commission may
approve the pending applications for MYLOTARG and BOSULIF in the EU
and whether and when any such other applications for MYLOTARG and
BOSULIF that may be pending or filed may be approved by regulatory
authorities, which will depend on the assessment by such regulatory
authorities of the benefit-risk profile suggested by the totality
of the efficacy and safety information submitted; uncertainties
regarding the commercial success of MYLOTARG and BOSULIF; decisions
by regulatory authorities regarding labeling and other matters that
could affect the availability or commercial potential of MYLOTARG
and BOSULIF; 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, 2017 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 Orpha.net. The portal for rare diseases and orphan drugs.
Accessed February 2018.
http://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=519
2 Leukemia & Lymphoma Society, Acute Myeloid Leukemia
Booklet. Developed 2011. Accessed February 2018.
https://www.lls.org/sites/default/files/file_assets/aml.pdf
3 American Cancer Society. What is Chronic Myeloid
Leukemia? http://www.cancer.org/acs/groups/cid/documents/webcontent/003112-pdf.pdf.
Accessed February 2018.
4 GLOBOCAN Online Analysis/Prediction.
http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=12280&Text-c=Leukaemia&pYear=8&type=0&window=1&submit=%C2%A0Execute.
Accessed February 2018.
5 European Treatment and Outcome Study.
https://www.eutos.org/content/registry/index_eng.html. Accessed
February 2018.
6 Griffin JD, Linch D, Sabbath K, et al: A monoclonal antibody
reactive with normal and leukemic human myeloid progenitor cells.
Leuk Res. 8: 521-534, 1984 CrossRefMedline.
7 Tanaka M, Kano Y, et al. The cytotoxic effects of gemtuzumab
ozogamicin (Mylotarg) in combination with conventional antileukemic
agents by isobologram Analysis In Vitro. Anticancer Research. 2009;
29: 4589-4596.
8 O’Hear C, Heiber JF, Schubert I, Fey G, Geiger TL. Anti-CD33
chimeric antigen receptor targeting of acute myeloid leukemia.
Haematologica. 2015;100(3):336-344.
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Pfizer Inc.Media:Jessica Smith, 212-733-6213orInvestor
Contact:Ryan Crowe, 212-733-8160
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