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Pfizer’s Ibrance Receives FDA Regular Approval and Expanded Indication for Metastatic Breast Cancer

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, YouTube and like us on Facebook at Facebook.com/Pfizer.

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