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June 27, 2018 12:00 am ET

LYNPARZA Met Primary Endpoint of Progression-Free Survival in Women with BRCA-Mutated Advanced Ovarian Cancer and Showed a Safety Profile Consistent with Previous Trials

AstraZeneca and Merck’s LYNPARZA is the Only PARP Inhibitor to Demonstrate Significant Activity in the First-Line Maintenance Setting

AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States
and Canada, today announced positive results from the randomized,
double-blinded, placebo-controlled, Phase 3 SOLO-1 trial of LYNPARZA^®
(olaparib) tablets.

Women with BRCA-mutated (BRCAm) advanced ovarian cancer
treated first-line with LYNPARZA maintenance therapy had a statistically
significant and clinically meaningful improvement in progression-free
survival (PFS) compared to placebo. The safety and tolerability profile
of LYNPARZA was consistent with previous trials. Based upon these data,
AstraZeneca and Merck plan to initiate discussions with health
authorities regarding regulatory submissions.

Sean Bohen, executive vice president, global medicines development and
chief medical officer at AstraZeneca, said, “For the first time, we see
a significant and clinically impactful improvement in progression-free
survival in the first-line maintenance setting for women with BRCA-mutated
ovarian cancer treated with a PARP inhibitor. The SOLO-1 data reinforce
the importance of knowing BRCA status at diagnosis, as this may
enable women with BRCA-mutated ovarian cancer to receive LYNPARZA
earlier. We would like to thank the investigators, hospitals and most of
all the patients who took part in this trial, without whom medical
advancements would not be possible.”

Dr. Roy Baynes, senior vice president and head of global clinical
development, chief medical officer, Merck Research Laboratories, said,
“Building on the strong data we’ve seen with LYNPARZA to date, the data
from SOLO-1 reinforce LYNPARZA’s ability to provide meaningful disease
control with a well-characterized safety and tolerability profile. We
look forward to presenting the full data set for SOLO-1 at a future
medical meeting and working with the regulatory authorities to bring
LYNPARZA to women with ovarian cancer in the first-line maintenance
setting as quickly as possible.”

LYNPARZA is not currently FDA-approved for 1st-line ovarian maintenance
treatment. LYNPARZA is indicated for the maintenance treatment of
recurrent ovarian cancer in response to platinum-based chemotherapy
regardless of BRCA mutation status, and for the treatment of advanced
ovarian cancer patients with a gBRCA-mutation previously treated with
three or more lines of chemotherapy. Physicians should select advanced
ovarian cancer patients for therapy based on a FDA-approved companion
diagnostic. Please see Indications for LYNPARZA

^®

(olaparib)
100 mg in the U.S. below.

Additionally, the ongoing GINECO/ENGOTov25 Phase 3 trial, PAOLA-1, is
testing the effect of LYNPARZA in combination with bevacizumab as a
first-line maintenance treatment in women with newly diagnosed advanced
ovarian cancer, regardless of their BRCA status. Results are
expected in 2019.

Indications for LYNPARZA

^®

(olaparib) 100 mg
in the U.S.

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

For the maintenance treatment of adult patients with recurrent
epithelial ovarian, fallopian tube, or primary peritoneal cancer, who
are in complete or partial response to platinum-based chemotherapy.

For the treatment of adult patients with deleterious or suspected
deleterious germline BRCA-mutated (gBRCAm) advanced
ovarian cancer who have been treated with 3 or more prior lines of
chemotherapy. Select patients for therapy based on an FDA-approved
companion diagnostic for LYNPARZA.

In patients with deleterious or suspected deleterious gBRCAm, human
epidermal growth factor receptor 2 (HER2)-negative metastatic breast
cancer who have previously been treated with chemotherapy in the
neoadjuvant, adjuvant or metastatic setting. Patients with hormone
receptor (HR)-positive breast cancer should have been treated with a
prior endocrine therapy or be considered inappropriate for endocrine
treatment. Select patients for therapy based on an FDA-approved
companion diagnostic for LYNPARZA.

Important Safety Information for LYNPARZA

^®


(olaparib) tablets 100 mg

Contraindications

There are no contraindications for LYNPARZA.

Warnings and Precautions

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
(olaparib) 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 treatment.

Females

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.

Males

Advise male patients with female partners of reproductive potential or
who are pregnant to use effective contraception during treatment and for
3 months following the last dose of LYNPARZA and to not donate sperm
during this time.

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 (olaparib) 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 (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 (25%).

Adverse Reactions—gBRCAm, HER2-Negative Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD
were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%),
vomiting (30%), neutropenia (27%), respiratory tract infection (27%),
leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD
were: decrease in hemoglobin (82%), decrease in lymphocytes (73%),
decrease in leukocytes (71%), increase in mean corpuscular volume (71%),
decrease in absolute neutrophil count (46%), and decrease in platelets
(33%).

Drug Interactions

Anticancer Agents: Clinical studies of LYNPARZA 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 (olaparib). If a moderate inducer cannot be
avoided, there is a potential for decreased efficacy of LYNPARZA.

Use In Specific Populations

Lactation: No data are available regarding the presence of
olaparib in human milk, its effects on the breastfed infant or 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.

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

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).

About SOLO-1

SOLO-1 is a Phase 3 randomized, double-blinded, placebo-controlled,
multi-center trial to evaluate the efficacy and safety of LYNPARZA
tablets as first-line maintenance monotherapy compared with placebo, in
patients with BRCA-mutated (BRCAm) advanced ovarian
cancer. The trial randomized 391 patients with a deleterious or
suspected deleterious BRCA1 or BRCA2 mutation who were in
clinical complete or partial response following platinum-based
chemotherapy. Eligible patients were randomized (2:1) to receive
LYNPARZA 300 mg tablets twice daily or placebo tablets twice daily. The
primary endpoint was progression-free survival (PFS) and key secondary
endpoints included time to second disease progression or death (PFS2)
and overall survival (OS).

About Ovarian Cancer

Worldwide, ovarian cancer is the seventh most common cancer and the
eighth leading cause of cancer death in women. The five-year survival
rate for ovarian cancer worldwide is 30-40 percent. In 2012, there were
nearly 239,000 new cases diagnosed and around 152,000 deaths.

Approximately 20,000 women in the United States are diagnosed with
ovarian cancer (including ovarian, fallopian tube and primary peritoneal
cancers) each year. Among women in the United States, it is the ninth
most common cancer and the fifth leading cause of cancer death.

The risk of developing ovarian cancer is increased in women with
specific inherited genetic abnormalities, including BRCA
mutations.

For newly-diagnosed, advanced ovarian cancer, the primary aim of
treatment is to delay progression of the disease for as long as possible
and maintain the patient’s quality of life, with the intent of achieving
complete remission or cure.

About BRCA Mutations

BRCA1 and BRCA2 are human genes that produce proteins
responsible for repairing damaged DNA and play an important role in
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
and cells become unstable. As a result, cells are more likely to develop
additional genetic alterations that can lead to cancer.

About LYNPARZA

LYNPARZA was the first-in-class PARP inhibitor and the first targeted
treatment to potentially exploit DNA damage response (DDR) pathway
deficiencies, such as BRCA mutations, to preferentially kill
cancer cells. Specifically, in vitro studies have shown that
LYNPARZA-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 being tested in a range of
DDR-deficient tumor types.

LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck, is approved for advanced ovarian cancer and
metastatic breast cancer and has been used in over 20,000 patients
worldwide. LYNPARZA has a broad and advanced clinical trial development
program, and AstraZeneca and Merck are working together to deliver it as
quickly as possible to more patients across multiple cancer types.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck, known as MSD outside the United
States and Canada, announced a global strategic oncology collaboration
to co-develop and co-commercialize LYNPARZA, the world’s first PARP
inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for
multiple cancer types. Working together, the companies will develop
LYNPARZA and selumetinib in combination with other potential new
medicines and as monotherapies. 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, the potential
to bring new hope to people with cancer drives our purpose and
supporting accessibility to our cancer medicines is our commitment.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the largest development
programs in the industry across more than 30 tumor types. We also
continue to strengthen our portfolio through strategic acquisitions and
are prioritizing the development of several promising oncology
candidates with the potential to improve the treatment of advanced
cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

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 www.merck.com
and connect with us on Twitter, Facebook, Instagram,
YouTube
and LinkedIn.

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“company”) includes “forward-looking statements” within the meaning of
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Please see complete 

Prescribing
Information

for LYNPARZA (olaparib), including Patient
Information (Medication Guide)

Merck
Media:
Pamela Eisele, (267) 305-3558
Michael Close, (267) 305-1211
or
Investor:
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