Pfizer Receives Positive CHMP Opinion for TALZENNA® (talazoparib) for Patients with Inherited (Germline) BRCA-Mutated Locally Advanced or Metastatic Breast Cancer

April 29, 2019 Off By BusinessWire

Positive opinion based on results from largest Phase 3 trial
performed to date of a PARP inhibitor in gBRCA-mutated advanced breast
cancer

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)
adopted a positive opinion recommending TALZENNA^®
(talazoparib), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, be
granted marketing authorization in the European Union (EU). The
indication the CHMP adopted is for TALZENNA as monotherapy for the
treatment of adult patients with germline breast cancer susceptibility
gene (gBRCA)1/2-mutations, who have human epidermal growth factor
receptor 2-negative (HER2-) locally advanced (LA) or metastatic breast
cancer (MBC). Patients should have been previously treated with an
anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or
metastatic setting unless patients were not suitable for these
treatments. Patients with hormone receptor-positive (HR+) breast cancer
should have been treated with a prior endocrine-based therapy, or be
considered unsuitable for endocrine-based therapy.

The positive CHMP opinion of TALZENNA follows the medicine’s approval by
the U.S. Food and Drug Administration (FDA) in October 2018.¹

“There is a pressing need for new, effective medicines that are
specifically developed for patients with an inherited BRCA
mutation who are often diagnosed at a younger age and have limited
options for the treatment of advanced-stage disease,” said Chris
Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global
Product Development. “Results from the EMBRACA trial provide evidence
supporting the use of TALZENNA in these patients, and we look forward to
working with the European Commission to potentially offer an alternative
treatment option to chemotherapy.”

The CHMP’s opinion for TALZENNA, which was acquired as part of Pfizer’s
acquisition of Medivation, will now be reviewed by the European
Commission. The Marketing Authorization Application was submitted based
on results from the EMBRACA trial, the largest Phase 3 trial performed
to date of a PARP inhibitor in patients with gBRCA-mutated LA or
MBC. This Phase 3, open-label, randomized trial evaluated once-daily
TALZENNA compared to physician’s choice standard chemotherapy
(capecitabine, eribulin, gemcitabine or vinorelbine) in patients with an
inherited BRCA1/2 mutation and triple-negative or HR+/HER2- LA or
MBC who may have received up to three prior cytotoxic chemotherapy
regimens for their advanced disease. A total of 431 patients were
enrolled at 145 sites in 16 countries, including 190 patients in
European countries such as Belgium, France, Germany, Ireland, Italy,
Poland, Spain and the United Kingdom.

About talazoparib

Talazoparib is an inhibitor of PARP enzymes, which play a role in DNA
repair. Preclinical studies suggest that talazoparib may work by
blocking PARP enzyme activity and trapping PARP at the site of DNA
damage, leading to decreased cancer cell growth and cancer cell death.
Talazoparib anti-tumor activity also was observed in mouse models of
human breast cancer that expressed mutated or non-mutated BRCA1/2.¹

In addition to gBRCA-mutated LA or MBC, talazoparib also is being
evaluated in several ongoing clinical trials in breast and other
cancers, including early triple-negative breast cancer and prostate
cancer, as well as other novel combinations with targeted therapies and
studies with immunotherapy in various solid tumors.

Indication in the U.S.

TALZENNA^®(talazoparib) is approved in the U.S. for the
treatment of adult patients with deleterious or suspected deleterious
germline breast cancer susceptibility gene (gBRCA)-mutated human
epidermal growth factor receptor 2-negative (HER2-), locally advanced or
metastatic breast cancer. Select patients for therapy based on an
FDA-approved companion diagnostic for TALZENNA.¹

TALZENNA^® (talazoparib) Important Safety
Information from the U.S. Prescribing Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) have
been reported in patients who received TALZENNA. Overall, MDS/AML have
been reported in 2 out of 584 (0.3%) solid tumor patients treated with
TALZENNA in clinical studies.

Myelosuppression consisting of anemia, leukopenia/neutropenia,
and/or thrombocytopenia have been reported in patients treated with
TALZENNA. Grade ≥3 anemia, neutropenia, and thrombocytopenia were
reported, respectively, in 39%, 21%, and 15% of patients receiving
TALZENNA. Discontinuation due to anemia, neutropenia, and
thrombocytopenia occurred, respectively, in 0.7%, 0.3%, and 0.3% of
patients.

Monitor complete blood counts for cytopenia at baseline and
monthly thereafter. Do not start TALZENNA until patients have adequately
recovered from hematological toxicity caused by previous therapy. If
hematological toxicity occurs, dose modifications (dosing interruption
with or without dose reduction) are recommended. With respect to
MDS/AML, for prolonged hematological toxicities, interrupt TALZENNA
and monitor blood counts weekly until recovery. If the levels have not
recovered after 4 weeks, refer the patient to a hematologist for further
investigations. If MDS/AML is confirmed, discontinue TALZENNA.

TALZENNA can cause fetal harm when administered to pregnant
women. Advise women of reproductive potential to use effective
contraception during treatment and for at least 7 months following the
last dose. A pregnancy test is recommended for females of reproductive
potential prior to initiating TALZENNA treatment. Advise male patients
with female partners of reproductive potential or who are pregnant to
use effective contraception during treatment with TALZENNA and for at
least 4 months after receiving the last dose. Based on animal studies,
TALZENNA may impair fertility in males of reproductive potential. Advise
women not to breastfeed while taking TALZENNA and for at least 1 month
after receiving the last dose because of the potential for serious
adverse reactions in nursing infants.

The most common adverse reactions (≥20%) of any grade for
TALZENNA vs chemotherapy were fatigue (62% vs 50%), anemia (53% vs 18%),
nausea (49% vs 47%), neutropenia (35% vs 43%), headache (33% vs 22%),
thrombocytopenia (27% vs 7%), vomiting (25% vs 23%), alopecia (25% vs
28%), diarrhea (22% vs 26%), and decreased appetite (21% vs 22%).

The most frequently reported Grade ≥3 adverse reactions (≥5%)
for TALZENNA vs chemotherapy were anemia (39% vs 5%), neutropenia (21%
vs 36%), and thrombocytopenia (15% vs 2%).

The most common lab abnormalities (≥25%) for TALZENNA vs
chemotherapy were decreases in hemoglobin (90% vs 77%), leukocytes (84%
vs 73%), lymphocytes (76% vs 53%), neutrophils (68% vs 70%), platelets
(55% vs 29%), and calcium (28% vs 16%) and increases in glucose (54% vs
51%), aspartate aminotransferase (37% vs 48%), alkaline phosphatase (36%
vs 34%), and alanine aminotransferase (33% vs 37%).

Coadministration with P-gp inhibitors or BCRP inhibitors
may increase TALZENNA exposure. If coadministering with the P-gp
inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, or
verapamil is unavoidable, reduce the TALZENNA dose to 0.75 mg once
daily. When the P-gp inhibitor is discontinued, increase the TALZENNA
dose (after 3–5 half-lives of the P-gp inhibitor) to the dose used prior
to the initiation of the P-gp inhibitor. When co-administering TALZENNA
with other known P-gp inhibitors or BCRP inhibitors, monitor patients
for potential increased adverse reactions.

For patients with moderate renal impairment, the recommended dose
of TALZENNA is 0.75 mg once daily. No dose adjustment is required for
patients with mild renal impairment. TALZENNA has not been studied in
patients with severe renal impairment or in patients requiring
hemodialysis.

TALZENNA has not been studied in patients with moderate or severe
hepatic impairment. No dose adjustment is required for patients with
mild hepatic impairment.

Please see full U.S. Prescribing Information and Patient Information for
TALZENNA^® (talazoparib) at www.TALZENNA.com.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we
believe we can make a meaningful difference in the lives of patients.
Today, Pfizer Oncology has an industry-leading portfolio of 18 approved
innovative cancer medicines and biosimilars across more than 20
indications, including breast, prostate, kidney, lung and hematology.
Pfizer Oncology is striving to change the trajectory of cancer.

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 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,
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DISCLOSURE NOTICE: The information contained in this release is as of
April 26, 2019. 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 TALZENNA
(talazoparib), including a potential indication in the EU and TALZENNA’s
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, uncertainties regarding the commercial
success of TALZENNA; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical trials,
regulatory submission dates, regulatory approval dates and/or launch
dates, as well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations and assessments by
regulatory authorities; whether regulatory authorities will be satisfied
with the design of and results from our clinical studies; whether and
when applications for TALZENNA may be filed in any other jurisdictions;
whether and when the European Commission may approve the pending
application for TALZENNA in the EU and whether and when any such other
applications for TALZENNA that may be pending or filed may be approved
by regulatory authorities, which will depend on myriad factors,
including making a determination as to whether the product’s benefits
outweigh its known risks and determination of the product’s efficacy
and, if approved, whether TALZENNA will be commercially successful;
decisions by regulatory authorities impacting labeling, manufacturing
processes, safety and/or other matters that could affect the
availability or commercial potential of TALZENNA; 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, 2018 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 TALZENNA® (talazoparib) Prescribing Information. New York.
NY: Pfizer Inc: 2018.