LYNPARZA is the Only PARP Inhibitor Approved
for Use Beyond Ovarian Cancer
LYNPARZA Reduced Risk of Disease Progression
or Death by 42 Percent Compared to Standard of Care
Chemotherapy
AstraZeneca and Merck (NYSE:MRK), known as MSD outside the
United States and Canada, today announced that the U.S. 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.
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 outside of
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.”
Dr. Roy Baynes, senior vice president and head of global
clinical development, chief medical officer, Merck Research
Laboratories, said, “This additional approval for LYNPARZA, based
on the compelling data from the OlympiAD trial, represents an
important advance for women with germline BRCA-mutated
HER2-negative metastatic breast cancer, 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 3 OlympiAD trial, which investigated LYNPARZA (olaparib)
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 percent (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 percent (95% CI
44-60), double the response rate for those in the chemotherapy arm
(n=66), which was 23 percent (95% CI 13-35). Additionally, patients
experienced a confirmed complete response rate of 7.8 percent for
LYNPARZA compared to 1.5 percent 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.
“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,” said
Dr. Susan M. Domchek, executive director of the Basser Center for
BRCA at the Abramson Cancer Center of the University of
Pennsylvania, and national leader on the OlympiAD trials. “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 U.S. 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 mutation.”
The most common adverse reactions 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 percent compared
to the chemotherapy arm, which was 8 percent. Please see
Important Safety Information below.
This is the third indication approved for LYNPARZA (olaparib) in
the U.S., where it has been used to treat nearly 4,000 advanced
ovarian cancer patients. 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.
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. 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 reproductive potential or who
are pregnant to use effective contraception during treatment and
for 3 months following the last dose of LYNPARZA (olaparib) 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
(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, 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).
Dosing and Administration
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.
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.
NOTES TO EDITORS
About OlympiAD
OlympiAD is a randomized, open-label, multicenter phase 3 trial
assessing the efficacy and safety of LYNPARZA tablets (300 mg twice
daily) compared to physician’s choice of chemotherapy in 302
patients with HER2-negative metastatic breast cancer with gBRCA1 or
gBRCA2 mutations, which are confirmed or suspected to be
deleterious. The international trial was conducted in 19 countries
across Europe, Asia, North America and South America.
Patients in the OlympiAD trial had HER2-negative gBRCA1- or
gBRCA2-mutated breast cancer, which was HR+ or triple negative, and
received LYNPARZA (olaparib) for metastatic disease. Approximately
half of the patients in the LYNPARZA and chemotherapy arm of the
trial were HR+ (n=152), and approximately half were triple negative
(n=150). Among the 205 patients treated with LYNPARZA, the median
age was 44 years (range: 22 to 76). Before enrollment, patients had
prior treatment with an anthracycline (unless contraindicated) and
a taxane chemotherapy either in the neoadjuvant, adjuvant or
metastatic setting and no more than two prior lines of chemotherapy
for metastatic disease. HR+ patients had received at least one
endocrine medicine or were not eligible for endocrine medicines.
Prior treatments with endocrine medicines were not counted as prior
lines of chemotherapy.
The primary endpoint of the trial was PFS as measured by a
Blinded Independent Central Review. Secondary endpoints included
overall survival, time to second progression or death, objective
response rate, and effect on health-related quality of life.
About Metastatic Breast Cancer
Three main receptors drive tumor growth in breast cancer:
Progesterone Receptors (PR), estrogen receptors (ER) and HER2
receptors. A patient’s breast cancer will test either negative or
positive for these three receptors. If a tumor tests positive for
PR and/or ER, it is considered HR+. If a tumor tests negative for
all three receptors, it is considered triple negative.
MBC is the most advanced stage of breast cancer (Stage IV), and
occurs when cancer cells have spread beyond the initial tumor site
to other parts of the body outside of the breast.
Despite the increase in treatment options during the past three
decades, there is currently no cure for patients diagnosed with MBC
and only 26.9 percent of patients survive five years after
diagnosis. 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.
It is estimated that in 2018, there will be approximately
155,000 women in the U.S. living with MBC, and this number is
projected to increase to approximately 160,000 by the year
2020.
About Germline BRCA Mutations
BRCA1 and BRCA2 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, 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 FDA-approved oral poly ADP-ribose
polymerase (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.
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. 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
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.
Forward-Looking Statement of Merck & Co., Inc.,
Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J.,
USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline products that
the products will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends
toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk;
dependence on the effectiveness of the company’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in the company’s 2016
Annual Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s
Internet site (www.sec.gov).
Please see complete Prescribing Information
for LYNPARZA (olaparib), including Patient Information
(Medication Guide)
View source
version on businesswire.com: http://www.businesswire.com/news/home/20180112005486/en/
MerckMedia:Pamela Eisele, 267-305-3558Courtney Ronaldo,
908-442-5695orInvestors:Teri Loxam, 908-740-1986Michael DeCarbo,
908-740-1807
Merck (NYSE:MRK)
Historical Stock Chart
From Aug 2024 to Sep 2024
Merck (NYSE:MRK)
Historical Stock Chart
From Sep 2023 to Sep 2024