Pfizer’s Third U.S. Hematology Approval in Five Months
NEW YORK--(BUSINESS WIRE)--
Pfizer Inc. (NYSE:PFE) today announced the U.S. Food and Drug
Administration (FDA) approved a supplemental New Drug Application (sNDA)
to expand the indication for BOSULIF® (bosutinib) to include
adult patients with newly-diagnosed chronic phase Philadelphia
chromosome-positive chronic myelogenous leukemia (Ph+ CML). The sNDA was
reviewed and approved under the FDA’s Priority Review and accelerated
approval programs based on molecular and cytogenetic response rates.
Continued approval for this indication may be contingent upon
verification and confirmation of clinical benefit in an ongoing
long-term follow up trial. BOSULIF was first approved in September 2012
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.
“BOSULIF was Pfizer’s first treatment for hematologic malignancies, and
has since become an important treatment option for Ph+ CML patients who
are resistant or intolerant to previous therapy. This expanded
indication has the potential to make an even greater impact on the lives
of patients with CML,” said Liz Barrett, Global President, Pfizer
Oncology. “Today’s news marks the third FDA approval for a Pfizer
hematology medicine in just five months, a significant achievement that
reinforces our commitment to patients living with blood cancers.”
“Among patients with CML today, with the various treatment options
available, it is important to recognize the unique needs of each of my
CML patients and prescribe treatments that best meet those needs,” said
Jorge E. Cortes, M.D., The University of Texas MD Anderson Cancer
Center. “The efficacy and distinct tolerability profile of BOSULIF make
it an important and useful treatment option for newly diagnosed CML
patients.”
The approval was based on results from BFORE (Bosutinib trial in First
line chrOnic myelogenous leukemia tREatment), a randomized
multicenter, multinational, open-label Phase 3 study which showed
BOSULIF 400 mg was associated with a significantly higher rate of
patients achieving major molecular response (MMR) at 12 months (47.2%;
95% CI, 40.9-53.4) compared to the rate achieved in patients treated
with imatinib 400 mg (36.9%; 95% CI, 30.8-43.0), a current standard of
care (two-sided P=0.0200). Complete cytogenic response (CCyR) rate by 12
months was 77.2% (95% CI: 72.0, 82.5) for patients treated with BOSULIF
compared to 66.4% (95% CI: 60.4, 72.4) for patients treated with
imatinib (two-sided P=0.0075). The adverse events seen in the trial were
consistent with the known safety profile for BOSULIF. The most common
adverse reactions in newly diagnosed CML patients treated with BOSULIF
(incidence ≥20%) are diarrhea (70%), nausea (35%), thrombocytopenia
(35%), rash (34%), increased alanine aminotransferase (ALT) (31%),
abdominal pain (25%), and increased aspartate aminotransferase (AST)
(23%). For more information, please see Important Safety Information for
BOSULIF below.
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 and conducted 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. With this approval,
Avillion is eligible to receive milestone payments from Pfizer. Pfizer
retains all rights to commercialize BOSULIF globally.
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.1
Researchers estimate that by 2020, more than 412,000 people worldwide
will be diagnosed with leukemia (all types).2 CML accounts
for 10-15% of all incident leukemia cases.1,3 In the U.S.,
approximately 48,000 people are living with CML.4 Around
9,000 new CML cases were diagnosed in the U.S. in 2017.1
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 now indicated for the treatment of patients with
newly-diagnosed chronic phase Philadelphia chromosome-positive chronic
myelogenous leukemia (Ph+ CML) and 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). A 400
mg tablet was also recently approved by the FDA in addition to the
previously approved 100 mg and 500 mg strengths. The recommended dose
for newly-diagnosed patients is 400 mg orally once daily with food. For
patients who are resistant or intolerant to prior tyrosine kinase
inhibitor (TKI) therapy, the recommended dose is 500 mg orally once
daily with food.
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. The European
Medicines Agency (EMA) has also validated for review a Type II Variation
application for use of BOSULIF in the same patient population.
About the BFORE Study
BFORE (Bosutinib trial in First line chrOnic
myelogenous leukemia tREatment) is a randomized, multicenter,
open-label Phase 3 study designed to assess the effectiveness and safety
of BOSULIF® (bosutinib) as a first-line treatment for patients with
chronic phase Ph+ CML. The study enrolled 536 patients at multiple sites
in North America, Asia and Europe. Patients were randomized 1:1 to
receive BOSULIF 400 mg or imatinib 400 mg, a standard of care, for the
duration of the study. The primary outcome was to show superiority of
BOSULIF over imatinib at 12 months by comparing MMR, or the proportion
of patients in each arm whose levels of the Bcr-Abl1 kinase have dropped
below 0.1%.
IMPORTANT BOSULIF® (bosutinib) SAFETY 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 Prescribing Information here.
About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on those living with cancer. As a leader in oncology
speeding cures and accessible breakthrough medicines to patients, Pfizer
Oncology is helping to redefine life with cancer. Our strong pipeline of
biologics, small molecules and immunotherapies, 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 its breakthrough medicines. Because Pfizer
Oncology knows that success in oncology is not measured solely by the
medicines you manufacture, but rather by the meaningful partnerships you
make to have a more positive impact on people’s lives.
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 healthcare products. Our global portfolio
includes medicines and vaccines as well as many of the world's
best-known consumer healthcare products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
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DISCLOSURE NOTICE: The information contained in this release is as of
December 19, 2017. 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 BOSULIF
(bosutinib), and a new indication in the U.S. for the treatment of adult
patients with newly-diagnosed chronic phase Philadelphia
chromosome-positive chronic myelogenous leukemia, including its
potential benefits, that involves 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 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; uncertainties regarding the commercial success of
BOSULIF; whether and when any applications for the new indication may be
filed with regulatory authorities in any other jurisdictions; whether
and when the EMA will approve the Type II Variation application for
the potential new indication and whether and when regulatory authorities
in any other jurisdictions may approve any such other applications that
may be pending or filed, 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; decisions by
regulatory authorities regarding labeling and other matters that could
affect the availability or commercial potential of BOSULIF, including
the new indication; 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, 2016 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 American Cancer Society. What is Chronic Myeloid Leukemia? http://www.cancer.org/acs/groups/cid/documents/webcontent/003112-pdf.pdf.
Accessed August 2017.
2 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 December 2017.
3 Hochhaus, A. Educational Session: Managing Chronic Myeloid
Leukemia as a Chronic Disease. American Society of Hematology. 2011; 10:
1.
4 National Cancer Institute. Surveillance Epidemiology and
End Results (SEER) Cancer Stat Facts: Chronic Myeloid Leukemia (CML). https://seer.cancer.gov/statfacts/html/cmyl.html.
Accessed December 2017.
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Source: Pfizer Inc.