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 1st-line
maintenance setting
AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US
(Merck: known as MSD outside the US and Canada) today announced
positive results from the randomized, double-blinded,
placebo-controlled, Phase III SOLO-1 trial of LYNPARZA® (olaparib)
tablets (300 mg twice daily).
Women with BRCA-mutated (BRCAm) advanced ovarian cancer treated
1st-line with LYNPARZA maintenance therapy had a
statistically-significant and clinically-meaningful improvement in
progression-free survival 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 1st-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.”
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 reinforces 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
regulatory authorities to bring LYNPARZA to women with ovarian
cancer in the 1st-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 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.
Additionally, the ongoing GINECO/ENGOTov25 Phase III trial,
PAOLA-1, sponsored by ENGOT/GCIG, is testing the effect of LYNPARZA
in combination with bevacizumab as a 1st-line maintenance treatment
in women with newly-diagnosed advanced ovarian cancer, regardless
of their BRCA status. Results are expected in 2019.
LYNPARZA is a first-in-class PARP inhibitor approved in the US
for certain patients with recurrent ovarian and metastatic breast
cancer and has treated nearly 5,500 patients 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, including 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.
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 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 therapy. Select patients for therapy based on an
FDA-approved companion diagnostic for LYNPARZA.
Please see complete Prescribing Information,
including Patient Information (Medication Guide).
NOTES TO EDITORS
About SOLO-1
SOLO-1 is a Phase III randomized, double-blinded,
placebo-controlled multi-center trial to evaluate the efficacy and
safety of LYNPARZA tablets as 1st-line maintenance monotherapy
compared with placebo, in patients with 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 and secondary key endpoints
include time to second disease progression or death and overall
survival.
About Ovarian Cancer
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® (olaparib)
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
and is the foundation of AstraZeneca’s industry-leading portfolio
of compounds targeting DDR mechanisms in cancer cells.
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 & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the United States and Canada,
announced a global strategic oncology collaboration to co-develop
and co-commercialize olaparib, the world’s first PARP inhibitor,
and potential new medicine selumetinib, a MEK inhibitor, for
multiple cancer types. Working together, the companies will develop
olaparib and selumetinib in combination with other potential new
medicines and as monotherapies. Independently, the companies will
develop olaparib and selumetinib in combination with their
respective PD-L1 and PD-1 medicines.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly growing portfolio of new medicines that has the potential
to transform patients’ lives and the Company’s future. With at
least six new medicines to be launched between 2014 and 2020 and a
broad pipeline of small molecules and biologics in development, we
are committed to advance Oncology as one of AstraZeneca’s Four
Growth Platforms focused on lung, ovarian, breast and blood
cancers. In addition to our core capabilities, we actively pursue
innovative partnerships and investments that accelerate the
delivery of our strategy as illustrated by our investment in Acerta
Pharma in hematology.
By harnessing the power of four scientific platforms –
Immuno-Oncology, Tumor Drivers and Resistance, DDR and Antibody
Drug Conjugates – and by championing the development of
personalized combinations, AstraZeneca has the vision to redefine
cancer treatment and one day eliminate cancer as a cause of
death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas - Oncology, Cardiovascular, Renal &
Metabolism and Respiratory. The Company also is selectively active
in the areas of autoimmunity, neuroscience and infection.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit www.astrazeneca-us.com and follow us on
Twitter @AstraZenecaUS.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20180627005564/en/
Media InquiriesAstraZenecaMichele Meixell, +1
302-885-2677orStephanie Wiswall, +1 302-885-2677
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From Apr 2024 to May 2024
AstraZeneca (NYSE:AZN)
Historical Stock Chart
From May 2023 to May 2024