NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration (FDA) has approved a supplemental New Drug Application
(sNDA) for its first-in-class cyclin dependent kinase 4/6 (CDK 4/6)
inhibitor, IBRANCE® (palbociclib), based on the results from
the confirmatory Phase 3 trial PALOMA-2. The FDA action converts the
accelerated approval of IBRANCE to regular approval and broadens the
range of anti-hormonal therapy that may be administered with IBRANCE.
IBRANCE now is indicated in combination with an aromatase inhibitor,
expanding on its earlier indication in combination with letrozole, as
initial endocrine based therapy in postmenopausal women with hormone
receptor-positive (HR+), human epidermal growth factor receptor
2-negative (HER2-) advanced or metastatic breast cancer.
IBRANCE is the first CDK 4/6 inhibitor approved by the FDA. IBRANCE was
granted accelerated approval in combination with letrozole in February
2015 and regular approval in February 2016 for a second indication: the
treatment of HR+, HER2- advanced or metastatic breast cancer in
combination with fulvestrant in women with disease progression following
endocrine therapy. Today, IBRANCE plus letrozole is the most prescribed
FDA-approved oral combination treatment for HR+, HER2- metastatic breast
cancer.
“In the two years since its initial approval, IBRANCE has been
prescribed to more than 50,000 patients by more than 9,800 physicians in
the U.S.,” said Liz Barrett, global president and general manager,
Pfizer Oncology. “This important update to the IBRANCE label underscores
the strength of the data we continue to generate for IBRANCE. We are
proud of the impact this innovative medicine continues to have on
patients’ lives.”
The updated label is based on data including results from the Phase 3
PALOMA-2 trial, which evaluated IBRANCE as first-line therapy in
combination with letrozole for postmenopausal women with estrogen
receptor-positive (ER+), HER2- metastatic breast cancer. These data were
published in the November 17, 2016 issue of The New England Journal
of Medicine. PALOMA-2 demonstrated that the combination of IBRANCE
and letrozole significantly extended progression-free survival (PFS), or
the amount of time before tumor growth, compared with letrozole plus
placebo. The median PFS of the IBRANCE and letrozole combination
exceeded two years – making it the first treatment for this population
of women to do so in a Phase 3 study. The median PFS for women treated
with IBRANCE plus letrozole exceeded the median PFS for placebo plus
letrozole by more than 10 months (24.8 months [95% CI, 22.1, not
estimable] vs. 14.5 months [95% CI, 12.9, 17.1] for women treated with
letrozole plus placebo (HR=0.58 [95% CI, 0.46, 0.72], p<0.0001)), and
represented a 42% reduction in the risk of disease progression.
The warnings and precautions of IBRANCE include neutropenia and
embryo-fetal toxicity. Adverse reactions in PALOMA-2 were generally
consistent with the known adverse reaction profile for IBRANCE and no
major unexpected safety findings were observed. The most common grade
3/4 adverse reactions with IBRANCE plus letrozole versus placebo plus
letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%),
infections (7% vs 3%) and anemia (5% vs 2%). Febrile neutropenia was
reported in 2.5% of patients in the IBRANCE plus letrozole group and
none of the patients in the placebo plus letrozole group.
Palbociclib (IBRANCE) is the only treatment for HR+, HER2- metastatic
breast cancer with two category 1 recommendations from the National
Comprehensive Care Network (NCCN). On March 13, the NCCN updated their
recommendation for palbociclib plus letrozole as a first-line treatment
for postmenopausal women with HR+, HER2- metastatic breast cancer to a
category 1 recommendation.1 In addition, palbociclib plus
fulvestrant is recommended (category 1) for postmenopausal women with
HR+, HER2- metastatic breast cancer who have progressed on endocrine
therapy or premenopausal women receiving a luteinizing hormone-releasing
hormone (LHRH) agonist.1
The full prescribing information for IBRANCE can be found here.
IMPORTANT IBRANCE® (palbociclib) SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
Neutropenia was the most frequently reported adverse reaction in
PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased
neutrophil counts were reported in patients receiving IBRANCE plus
fulvestrant. Febrile neutropenia has been reported in 1.8% of patients
exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to
neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly
report any fever.
Monitor complete blood count prior to starting IBRANCE, at the beginning
of each cycle, on Day 15 of first 2 cycles and as clinically indicated.
Dose interruption, dose reduction, or delay in starting treatment cycles
is recommended for patients who develop Grade 3 or 4 neutropenia.
Based on the mechanism of action, IBRANCE can cause fetal harm.
Advise females of reproductive potential to use effective contraception
during IBRANCE treatment and for at least 3 weeks after the last dose.
IBRANCE may impair fertility in males and has the potential to
cause genotoxicity. Advise male patients with female partners of
reproductive potential to use effective contraception during IBRANCE
treatment and for 3 months after the last dose. Advise females to inform
their healthcare provider of a known or suspected pregnancy. Advise women
not to breastfeed during IBRANCE treatment and for 3 weeks after the
last dose because of the potential for serious adverse reactions in
nursing infants.
The most common adverse reactions (≥10%) of any grade reported in PALOMA-2
for IBRANCE plus letrozole vs placebo plus letrozole were
neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs
2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%),
stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash
(18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%),
vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs
6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).
The most frequently reported Grade ≥3 adverse reactions (≥5%) in
PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were
neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%),
and anemia (5% vs 2%).
Lab abnormalities of any grade occurring in PALOMA-2 for
IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97%
vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%),
decreased platelets (63% vs 14%), increased aspartate aminotransferase
(52% vs 34%), and increased alanine aminotransferase (43% vs 30%).
The most common adverse reactions (≥10%) of any grade reported in
PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant
were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs
31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%),
stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs
0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%),
decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).
The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3
for IBRANCE plus fulvestrant vs placebo plus fulvestrant were
neutropenia (66% vs 1%) and leukopenia (31% vs 2%).
Lab abnormalities of any grade occurring in PALOMA-3 for
IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC
(99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%),
decreased platelets (62% vs 10%), increased aspartate aminotransferase
(43% vs 48%), and increased alanine aminotransferase (36% vs 34%).
Avoid concurrent use of strong CYP3A inhibitors. If patients must
be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75
mg/day. If the strong inhibitor is discontinued, increase the IBRANCE
dose (after 3-5 half-lives of the inhibitor) to the dose used prior to
the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit
juice may increase plasma concentrations of IBRANCE and should be
avoided. Avoid concomitant use of strong CYP3A inducers. The dose
of sensitive CYP3A substrates with a narrow therapeutic index may
need to be reduced as IBRANCE may increase their exposure.
IBRANCE has not been studied in patients with moderate to
severe hepatic impairment or in patients with severe renal
impairment (CrCl <30 mL/min).
About IBRANCE® (palbociclib) 125 mg capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,2 which are key
regulators of the cell cycle that trigger cellular progression.3,4
In the U.S., IBRANCE is indicated for the treatment of HR+, HER2-
advanced or metastatic breast cancer in combination with an aromatase
inhibitor as initial endocrine based therapy in postmenopausal women,
or fulvestrant in women with disease progression following endocrine
therapy.
Including the U.S., IBRANCE is approved in more than 60 countries.
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 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 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,
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, Pfizer has 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 @PfizerNews,
LinkedIn,
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and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is as of
March 31, 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 IBRANCE
(palbociclib), 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, uncertainties
regarding the commercial success of IBRANCE; 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; whether regulatory authorities will
be satisfied with the design of and results from our clinical studies;
whether and when drug applications may be filed in any additional
jurisdictions for IBRANCE for potential HR+/HER2- metastatic breast
cancer indications or in any jurisdictions for any other potential
indications for IBRANCE; whether and when any such other applications
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; decisions by regulatory authorities regarding labeling and
other matters that could affect the availability or commercial potential
of IBRANCE; 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 National Comprehensive Cancer Network. NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines®): Breast Cancer.
Version 1.2017.
2 IBRANCE® (palbociclib) Prescribing Information. New York.
NY: Pfizer Inc: 2017.
3 Weinberg RA. pRb and Control of the Cell Cycle Clock. In:
Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland
Science; 2014:275-329.
4 Sotillo E, Grana X. Escape from Cellular Quiescence. In:
Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana
Press; 2010:3-22.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170331005718/en/
Contacts
Pfizer Inc.
Media:
Sally Beatty (US), 212-733-6566
Investors:
Ryan
Crowe, 212-733-8160
Source: Pfizer Inc.
Cet article IBRANCE® (palbociclib) Receives FDA Regular
Approval and Expanded Indication for First-Line HR+, HER2- Metastatic
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