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
NEW YORK--(BUSINESS WIRE)--
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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Source: Pfizer Inc.