LYNPARZA® (olaparib) Approved by US FDA in Germline BRCA-Mutated Metastatic Breast Cancer

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LYNPARZA is the first and only PARP inhibitor approved for use
beyond ovarian cancer

LYNPARZA reduced the risk of disease progression or death by 42%
compared to standard of care chemotherapy

AstraZeneca and Merck (Merck: known as MSD outside the US and Canada)
today announced that the US Food and Drug Administration (FDA) has
approved LYNPARZA® (olaparib), for use in patients
with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm),
human epidermal growth factor receptor 2 (HER2)-negative metastatic
breast cancer who have been previously treated with chemotherapy in the
neoadjuvant, adjuvant or metastatic setting. Patients with hormone
receptor positive (HR+) breast cancer should have been treated with a
prior endocrine therapy or be considered inappropriate for endocrine
therapy. Patients are selected for therapy based on an FDA-approved
companion diagnostic from Myriad Genetics.1

Dave Fredrickson, Executive Vice President, Head of the Oncology
Business Unit, AstraZeneca, said: “This new approval for LYNPARZA makes
it the first and only PARP inhibitor approved in metastatic breast
cancer, and the only PARP inhibitor approved beyond ovarian cancer. This
is significant for breast cancer patients, as the identification of BRCA
status, in addition to hormone receptor and HER2 status, becomes a
potentially critical step in the management of their disease.”

Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, Merck Research Laboratories, said:
“This additional approval for LYNPARZA represents an important advance
for women with HER2-negative metastatic breast cancer with a germline BRCA
mutation, which is a difficult-to-treat cancer. Moreover, this approval
adds further impetus to our important collaboration with AstraZeneca in
developing cancer therapies.”

The approval was based on data from the randomized, open-label, Phase
III OlympiAD trial
, which investigated LYNPARZA versus physician’s
choice of chemotherapy (capecitabine, eribulin or vinorelbine). In the
trial, LYNPARZA significantly prolonged progression-free survival (PFS)
compared with chemotherapy, and reduced the risk of disease progression
or death by 42% (HR 0.58; 95% CI 0.43-0.80; P=0.0009 median 7.0 vs 4.2
months). Patients with measurable disease taking LYNPARZA (n=167)
experienced an objective response rate of 52% (95% CI 44-60), double the
response rate for those in the chemotherapy arm (n=66) which was 23%
(95% CI 13-35). Additionally, patients experienced a confirmed complete
response rate of 7.8% for LYNPARZA compared to 1.5% for the chemotherapy
arm. The data from the OlympiAD trial can be found in the June 2017
issue of the New
England Journal of Medicine

Dr. Susan M. Domchek, Executive Director of the Basser Center for BRCA
at the Abramson Cancer Center of the University of Pennsylvania, and a
national leader on the OlympiAD trials said: “Patients diagnosed with BRCA-related
metastatic breast cancer are often younger than other breast cancer
patients, and their disease is often much more aggressive and difficult
to treat. While there is currently no cure for metastatic breast cancer,
today’s approval offers a new, targeted option that may help to delay
disease progression for these patients.”

Sue Friedman, Executive Director and founder of the nonprofit
organization, Facing Our Risk of Cancer Empowered (FORCE), said: “We
know there are limited treatment options for patients with metastatic
breast cancer. For the portion of the 155,000 women in the US living
with metastatic breast cancer who have an inherited BRCA
mutation, today’s news is encouraging. By undergoing genetic testing for BRCA
mutations, we can gain critical information that will inform
personalized treatment options specifically for women with this

The most common adverse reactions (≥20%) in the OlympiAD trial of
patients who received LYNPARZA were nausea (58%), anemia (40%), fatigue
(including asthenia) (37%), vomiting (30%), neutropenia (27%),
respiratory tract infection (27%), leukopenia (25%), diarrhea (21%) and
headache (20%). The percentage of patients who discontinued treatment in
the LYNPARZA arm was 5% compared to the chemotherapy arm which was 8%. Please
see Important Safety Information below.

This is the third indication approved for LYNPARZA in the US, where it
has been used to treat nearly 4,000 advanced ovarian cancer patients.1,3
LYNPARZA has a broad clinical development program, and
AstraZeneca and Merck are working together to deliver LYNPARZA as
quickly as possible to more patients across multiple settings, including
breast, ovarian, prostate and pancreatic cancers.4-7

Sustainable and Ongoing Externalization Revenue

Under the oncology collaboration with Merck, announced in July 2017,
AstraZeneca is potentially eligible for more than $6 billion of future
Sustainable and Ongoing Externalization Revenue in the form of
sales-related and approval-related payments in addition to option
payments until 2019. Following this new approval for LYNPARZA,
AstraZeneca will receive $70 million in Sustainable and Ongoing
Externalization Revenue.


There are no contraindications for

Myelodysplastic Syndrome/Acute
Myeloid Leukemia (MDS/AML):
Occurred in <1.5% of patients exposed to
LYNPARZA monotherapy, and the majority of events had a fatal outcome.
The duration of therapy in patients who developed secondary MDS/AML
varied from <6 months to >2 years. All of these patients had previous
chemotherapy with platinum agents and/or other DNA-damaging agents,
including radiotherapy, and some also had a history of more than one
primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood count for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt LYNPARZA and monitor blood count
weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer
the patient to a hematologist for further investigations, including bone
marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA
if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and
some cases were fatal. If patients present with new or worsening
respiratory symptoms such as dyspnea, cough, and fever, or a
radiological abnormality occurs, interrupt LYNPARZA treatment and
initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is
confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and
findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is
recommended for females of reproductive potential prior to initiating

Advise females of reproductive potential of the
potential risk to a fetus and to use effective contraception during
treatment and for 6 months following the last dose.

Advise male patients with female partners of

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