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October 21, 2018 9:30 am ET

60 Percent of Patients Receiving LYNPARZA Remained Progression-Free at Three Years Compared to 27 Percent on Placebo Following Platinum-Based Chemotherapy

LYNPARZA Is the Only PARP Inhibitor to Demonstrate an Improvement in Progression-Free Survival in First-Line Maintenance Treatment for Newly-Diagnosed, Advanced Ovarian Cancer

KENILWORTH, N.J.–(BUSINESS WIRE)–AstraZeneca and Merck (NYSE:MRK), known as MSD outside the United States
and Canada, today announced detailed results from the Phase 3 SOLO-1
trial testing LYNPARZA 300 mg tablets twice daily as a maintenance
treatment for patients with newly-diagnosed advanced BRCA-mutated
(BRCAm) ovarian cancer who were in complete or partial response
following first-line standard platinum-based chemotherapy.

Results of the trial confirm the statistically-significant and
clinically-meaningful improvement in progression-free survival (PFS) for
LYNPARZA as compared to placebo, reducing the risk of disease
progression or death by 70 percent (HR=0.30 [95% CI, 0.23-0.41];
p<0.001). At 41 months of follow-up, the median PFS for patients treated
with LYNPARZA was not reached compared to 13.8 months for patients
treated with placebo. Of those receiving LYNPARZA, 60.4 percent remained
progression-free at 36 months, compared to 26.9 percent of women in the
placebo arm. The data were presented at the Presidential Symposium of
the ESMO 2018 Congress in Munich, Germany and published simultaneously
online in the New England Journal of Medicine (NEJM).

Summary of PFS as Assessed by Investigators

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Sean Bohen, executive vice president, Global Medicines Development and
chief medical officer at AstraZeneca, said, “There is currently a
significant unmet need in the treatment of advanced ovarian cancer
because 70 percent of women relapse within the first three years after
their initial treatment. The remarkable results of the SOLO-1 trial,
which showed that 60 percent of women with newly-diagnosed, advanced BRCA-mutated
ovarian cancer remained progression-free at three years, highlight the
potential of LYNPARZA as a first-line maintenance therapy in this
setting.”

Dr. Roy Baynes, senior vice president and head of Global Clinical
Development, chief medical officer, Merck Research Laboratories, said,
“Our collective goal in oncology research is to improve long-term
outcomes for people living with cancer. Based on the SOLO-1 trial
results, LYNPARZA is the only PARP inhibitor to have demonstrated a
significant and clinically-meaningful improvement in reducing the risk
of progression or death for newly-diagnosed patients with advanced BRCA-mutated
ovarian cancer following platinum-based chemotherapy. We are working
with regulatory authorities as quickly as possible to seek approval of
LYNPARZA for these patients.”

Kathleen Moore, co-principal investigator of the SOLO-1 trial and
associate director, Stephenson Cancer Center at The University of
Oklahoma, Oklahoma City, Oklahoma, said, “Women with ovarian cancer are
often diagnosed with advanced disease, which unfortunately is associated
with poor long-term survival rates. The newly-diagnosed setting is our
best opportunity to achieve a sustained remission, since once a
patient’s ovarian cancer recurs, it is typically incurable. The SOLO-1
results demonstrate the potential of LYNPARZA maintenance therapy
earlier in the treatment pathway and reinforce the importance of
identifying a patient’s BRCA mutation status at the time of
diagnosis – these results could change the way we treat women with
advanced BRCA-mutated ovarian cancer.”

The SOLO-1 safety profile was in line with that observed in prior
clinical trials. The most common adverse events (AEs) ≥ 20 percent were
nausea (77%), fatigue (64%), vomiting (40%), anemia (39%) and diarrhea
(34%). The most common ≥ Grade 3 AEs were anemia (22%) and neutropenia
(8%). Seventy-one percent of patients on LYNPARZA remained on the
recommended starting dose. Additionally, 88 percent of patients on
LYNPARZA continued treatment without an AE-related discontinuation.
Further, 48 percent of patients on LYNPARZA did not have a dose
interruption as a result of an AE.

Per SOLO-1 protocol guidelines, patients who demonstrated a complete
response (no radiological evidence of disease) at two years stopped
treatment with LYNPARZA; patients who demonstrated a partial response
and, who in the opinion of the treating physician can derive further
benefit from continuous treatment, were treated beyond two years.

AstraZeneca and Merck are exploring additional trials in ovarian cancer,
including the ongoing GINECO/ENGOTov25 Phase 3 trial, PAOLA-1. This
trial is testing the effect of LYNPARZA in combination with
bevacizumab as a maintenance treatment for patients with newly-diagnosed
advanced ovarian cancer regardless of their BRCA status. Results
are expected during the second half of 2019.

LYNPARZA is a first-in-class poly ADP-ribose polymerase (PARP) inhibitor
approved in the U.S. since 2014. 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
cancer types.

LYNPARZA is not currently FDA-approved for advanced BRCAm ovarian
cancer treatment in the first-line maintenance setting. 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 germline BRCA 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 complete indications below.

Important Safety Information

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
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 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. 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).

Indications

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.

Please see complete

Prescribing
Information

, including Patient Information (Medication Guide).

About the SOLO-1 Phase 3 Trial

SOLO-1 is a Phase 3, randomized, double-blind, placebo-controlled,
multi-center trial to evaluate the efficacy and safety of LYNPARZA
tablets (300 mg twice daily) as maintenance monotherapy compared
with placebo in newly-diagnosed patients with advanced BRCA-mutated
ovarian cancer following platinum-based chemotherapy. 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. Patients were randomized
(2:1) to receive LYNPARZA or placebo for up to two years or until
disease progression (at the investigator’s discretion). The primary
endpoint was investigator-assessed progression-free survival and key
secondary endpoints include time to second disease progression or death,
time to first subsequent treatment and overall survival.

About Ovarian Cancer

Approximately 20,000 women in the U.S. are diagnosed with ovarian cancer
(including ovarian, fallopian tube and primary peritoneal cancers) each
year. Among women in the U.S., 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.

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

^®

(olaparib)

LYNPARZA is 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, 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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