AstraZeneca and Merck Rapidly Advance LYNPARZA® (olaparib) in Japan With a Second Regulatory Submission


October 23, 2017 5:55 am ET

Potential to Offer a New Treatment Option for Patients With Germline BRCA-mutated, HER2-negative Metastatic Breast Cancer

KENILWORTH, N.J.–(BUSINESS WIRE)–AstraZeneca and Merck (NYSE:MRK), known as MSD outside the U.S. and
Canada, today announced that they have submitted a new drug application
(NDA) to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) for
the use of LYNPARZA
(olaparib) tablets in
unresectable or recurrent BRCA-mutated breast cancer, with a decision
expected in the second half of 2018.

The Japan NDA is based on the positive results from the Phase III
OlympiAD trial published in the New England Journal of Medicine.

This is the second NDA for LYNPARZA in Japan where the medicine is
currently under review for use in ovarian cancer, with a PMDA decision
for this indication anticipated in the first half of 2018.

LYNPARZA tablets are currently being tested in a range of tumor types in
addition to ovarian and breast, including prostate and pancreatic



To avoid substitution errors and overdose, do not substitute LYNPARZA (olaparib)
tablets with LYNPARZA capsules on a milligram-to-milligram basis
due to differences in the dosing and bioavailability of each
formulation. Recommended tablet dose is 300 mg, taken orally twice
daily, with or without food. Continue treatment until disease
progression or unacceptable toxicity. For adverse reactions, consider
dose interruption or dose reduction.


There are no contraindications for LYNPARZA.

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 of these
patients also had a history of previous cancer or bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood counts for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt LYNPARZA and monitor blood counts
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 treatment with LYNPARZA and
initiate prompt investigation. Discontinue LYNPARZA (olaparib) 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
treatment. Advise females of reproductive potential of the potential
risk to a fetus and to use effective contraception during treatment and
for 6 months after receiving the final dose.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA in the maintenance setting for SOLO-2: nausea
(76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%),
nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%),
diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache
(26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%),
vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract
infection (22%), constipation (22%), headache (21%), and decreased
appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA in the maintenance setting
(SOLO-2/Study 19
) were: increase in mean corpuscular volume
(89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes
(69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute
neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and
decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer
after 3 or more lines of chemotherapy
(pooled from 6 studies) were:
fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia
(34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection
(URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%),
and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer
after 3 or more lines of chemotherapy
(pooled from 6 studies) were:
decrease in hemoglobin (90%), increase in mean corpuscular volume (57%),
decrease in lymphocytes (56%), increase in serum creatinine (30%),
decrease in platelets (30%), and decrease in absolute neutrophil count


Anticancer Agents: Clinical studies of LYNPARZA (olaparib) in
combination with other myelosuppressive anticancer agents, including
DNA-damaging agents, indicate a potentiation and prolongation of
myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate
CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must
be co-administered, reduce the dose of LYNPARZA. Advise patients to
avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange
juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A
inducers when using LYNPARZA. If a moderate inducer cannot be avoided,
be aware of a potential for decreased efficacy of LYNPARZA.


Pediatric Use: The safety and efficacy of LYNPARZA have not been
established in pediatric patients.

Lactation: No data are available regarding the presence of
olaparib in human milk, the effects on the breastfed infant, or the
effects on milk production. Because of the potential for serious adverse
reactions in the breastfed infant, advise a lactating woman not to
breastfeed during treatment with LYNPARZA and for 1 month after
receiving the final dose.

Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild hepatic impairment (Child-Pugh
classification A). There are no data in patients with moderate or severe
hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary
in patients with mild renal impairment (CLcr 51-80 mL/min). In patients
with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose to
200 mg twice daily. There are no data in patients with severe renal
impairment or end-stage renal disease (CLcr ≤30 mL/min).

Please see complete Prescribing Information, including Patient
Information (Medication Guide)

About OlympiAD

OlympiAD is a randomized, open-label,
multicenter phase 3 trial assessing the efficacy and safety of LYNPARZA
(olaparib) tablets (300mg twice daily) compared to ‘physician’s
choice’ chemotherapy (capecitabine, vinorelbine, eribulin) in 302
patients with HER2-negative metastatic breast cancer with germline BRCA1
or BRCA2 mutations, which are predicted or suspected to be
deleterious. The international trial was conducted in 19 countries from
across Europe, Asia, North America and South America.




was the first FDA-approved oral poly ADP-ribose polymerase (PARP)
inhibitor that may exploit tumor DNA damage response (DDR) pathway
deficiencies to potentially kill cancer cells. Specifically, in
studies have shown that olaparib-induced cytotoxicity may
involve inhibition of PARP enzymatic activity and increased formation of
PARP-DNA complexes, resulting in DNA damage and cancer cell death.

LYNPARZA is the foundation of AstraZeneca’s industry-leading portfolio
of compounds targeting DDR mechanisms in cancer cells.

About Metastatic Breast Cancer

Approximately one in eight
women are diagnosed with breast cancer in the U.S. Of these
patients, approximately one-third are either diagnosed with or progress
to the metastatic stage of the disease. Despite treatment options
increasing during the past three decades, there is currently no cure for
patients diagnosed with metastatic breast cancer. Thus, the primary aim
of treatment is to slow progression of the disease for as long as
possible, improving or at least maintaining, a patient’s quality of life.

About Germline BRCA Mutations

are human genes that produce proteins responsible for repairing damaged
DNA and play an important role maintaining the genetic stability of
cells. When either of these genes is mutated, or altered, such that its
protein product either is not made or does not function correctly, DNA
damage may not be repaired properly. As a result, cells are more likely
to develop additional genetic alterations that can lead to cancer.

About the AstraZeneca and Merck Strategic Oncology Collaboration

July 27, 2017, AstraZeneca and Merck & Co., Inc., announced a global
strategic oncology collaboration to co-develop and co-commercialize
AstraZeneca’s LYNPARZA (olaparib), the world’s first and leading PARP
inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for
multiple cancer types. The collaboration is based on increasing evidence
that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors
for a range of tumor types. Working together, the companies will jointly
develop LYNPARZA and selumetinib in combination with other potential new
medicines and as a monotherapy. Independently, the companies will
develop LYNPARZA and selumetinib in combination with their respective
PD-L1 and PD-1 medicines.

Merck’s Focus on Cancer

Our goal is to translate
breakthrough science into innovative oncology medicines to help people
with cancer worldwide. At Merck, helping people fight cancer is our
passion and supporting accessibility to our cancer medicines is our
commitment. Our focus is on pursuing research in immuno-oncology and we
are accelerating every step in the journey – from lab to clinic – to
potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program evaluating our anti-PD-1 therapy across more than 30
tumor types. We also continue to strengthen our immuno-oncology
portfolio through strategic acquisitions and are prioritizing the
development of several promising immunotherapeutic candidates with the
potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit

About Merck

For more than a century, Merck, a leading global
biopharmaceutical company known as MSD outside of the United States and
Canada, has been inventing for life, bringing forward medicines and
vaccines for many of the world’s most challenging diseases. Through our
prescription medicines, vaccines, biologic therapies and animal health
products, we work with customers and operate in more than 140 countries
to deliver innovative health solutions. We also demonstrate our
commitment to increasing access to health care through far-reaching
policies, programs and partnerships. Today, Merck continues to be at the
forefront of research to advance the prevention and treatment of
diseases that threaten people and communities around the world –
including cancer, cardio-metabolic diseases, emerging animal diseases,
Alzheimer’s disease and infectious diseases including HIV and Ebola. For
more information, visit and connect
with us on TwitterFacebookInstagramYouTube
and LinkedIn.

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Pamela Eisele, 267-305-3558
Courtney Ronaldo, 908-740-6132
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898

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