a4496m
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of May
2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza approved
in the US as 1st-line maintenance
treatment
with
bevacizumab for HRD-positive advanced ovarian cancer
11 May 2020 07:00
BST
Lynparza approved in the US as 1st-line maintenance
treatment
with bevacizumab for HRD-positive advanced ovarian
cancer
Patients treated with Lynparza and bevacizumab lived without
disease progression for 37.2 months vs. 17.7 months median for
bevacizumab alone
One in two women with advanced ovarian cancer has an HRD-positive
tumour
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck
& Co., Inc. inside the US and Canada) today announced
that Lynparza (olaparib) in combination with bevacizumab
has been approved in the US for the maintenance treatment of adult
patients with advanced epithelial ovarian, fallopian tube or
primary peritoneal cancer who are in complete or partial response
to 1st-line platinum-based chemotherapy and whose cancer is
associated with homologous recombination deficiency (HRD) positive
status defined by either a deleterious or suspected deleterious
BRCA mutation, and/or genomic instability. Patients will be
selected for therapy based on an FDA-approved companion diagnostic
test.
The approval by the US Food and Drug Administration (FDA) was based
on a biomarker subgroup analysis of the Phase III PAOLA-1
trial which showed
that Lynparza in combination with bevacizumab maintenance
treatment reduced the risk of disease progression or death by 67%
(equal to a hazard ratio of 0.33). The addition
of Lynparza improved progression-free survival (PFS) to
a median of 37.2 months versus 17.7 months with bevacizumab alone
in patients with HRD-positive advanced ovarian
cancer.
Approximately one in two women with advanced ovarian cancer has an
HRD-positive tumour. For patients with advanced ovarian
cancer, the primary aim of 1st-line treatment is to delay disease
progression for as long as possible with the intent to achieve
long-term remission.
Isabelle Ray-Coquard, principal investigator of the PAOLA-1 trial
and medical oncologist, Centre Léon Bérard and President
of the GINECO group, said: "Ovarian cancer is a devastating
disease. The magnitude of benefit in HRD-positive patients in the
PAOLA-1 trial is impactful. The combination
of Lynparza and bevacizumab now provides women with
HRD-positive advanced ovarian cancer with a new standard of care
and I look forward to seeing this translate into clinical
practice."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "This approval represents another milestone
for Lynparza in patients with ovarian cancer. The median
progression-free survival of more than three years offers new hope
for more women to delay relapse in this difficult-to-treat disease.
These results further establish that HRD-positive is a distinct
subset of ovarian cancer, and HRD testing is now a critical
component for the diagnosis and tailoring of treatment for women
with advanced ovarian cancer."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Advances in understanding the role of biomarkers and PARP
inhibition have fundamentally changed how physicians treat this
aggressive type of cancer. Today's approval based on the PAOLA-1
trial highlights the importance of HRD testing at diagnosis to
identify those who may benefit from Lynparza in combination with bevacizumab as a
1st-line maintenance treatment."
The full results from the Phase III PAOLA-1 trial were
published in The
New England Journal of Medicine.
Regulatory reviews are currently underway in the EU, Japan and
other countries for Lynparza based on results from the PAOLA-1
trial. As part of a broad development
programme, Lynparza is being tested as a monotherapy and in
combination across multiple tumour types including as a potential
adjuvant treatment of patients with germline BRCA-mutated high-risk
HER2-negative primary breast cancer in the Phase III OlympiA
trial.
Financial considerations
Following this approval for Lynparza in the US, AstraZeneca will receive from MSD
$100m in Collaboration Revenue, anticipated to be booked by the
Company during the second quarter of 2020.
Ovarian cancer
Ovarian cancer is the eighth most common cause of death from cancer
in women worldwide.1 In
2018, there were nearly 300,000 new cases diagnosed and around
185,000 deaths.2 Most
women are diagnosed with advanced (Stage III or IV) ovarian cancer
and have a five-year survival rate of approximately
30%.3 Approximately
50% of ovarian cancers are HRD-positive including BRCA1/2
mutation. 4,5 Some
22% of ovarian cancers have a BRCA1/2 mutation.5
For patients with advanced ovarian cancer, the primary aim of
1st-line 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.6,7,8,9
In the US, bevacizumab was approved for use in combination with
chemotherapy for the 1st-line treatment of advanced ovarian cancer
in 2018. Within two years nearly half of all patients with advanced
ovarian cancer are receiving this combination
treatment.10
PAOLA-1
PAOLA-1 is a double-blind Phase III trial testing the efficacy and
safety of Lynparza in combination with bevacizumab vs.
bevacizumab alone, as a 1st-line maintenance treatment for newly
diagnosed advanced FIGO Stage III-IV high-grade serous or
endometroid ovarian, fallopian tube, or peritoneal cancer patients
who had a complete or partial response to 1st-line treatment with
platinum-based chemotherapy and bevacizumab. AstraZeneca and
MSD announced in August
2019 that the trial met
its primary endpoint of PFS.
Simultaneously, the Myriad Genetics myChoice CDx test has been
approved in the US as a companion diagnostic
for Lynparza in this new indication.
Homologous recombination deficiency
HRD, which defines a sub-group of ovarian cancer, encompasses a
wide range of genetic abnormalities, including BRCA mutations and
beyond. As with BRCA gene mutations, HRD interferes with normal
cell DNA repair mechanisms and confers sensitivity to PARP
inhibitors including Lynparza.5
Lynparza
Lynparza (olaparib) is a
first-in-class PARP inhibitor and the first targeted treatment to
block DNA damage response (DDR) in cells/tumours harbouring a
deficiency in homologous recombination repair, such as mutations in
BRCA1 and/or BRCA2. Inhibition of PARP
with Lynparza leads
to the trapping of PARP bound to DNA single-strand breaks, stalling
of replication forks, their collapse and the generation of DNA
double-strand breaks and cancer cell
death. Lynparza is
being tested in a range of PARP-dependent tumour types with defects
and dependencies in the DDR pathway.
Lynparza is currently
approved in a number of countries, including those in the EU, for
the maintenance treatment of platinum-sensitive relapsed ovarian
cancer. It is approved in the US, the EU, Japan, China, and several
other countries as 1st-line maintenance treatment of BRCA-mutated
advanced ovarian cancer following response to platinum-based
chemotherapy. It is also approved in the US, Japan, and a number of
other countries for germline BRCA-mutated, HER2-negative,
metastatic breast cancer, previously treated with chemotherapy; in
the EU, this includes locally advanced breast
cancer. Lynparza is approved in the US and several other
countries for the treatment of germline BRCA-mutated metastatic
pancreatic cancer. Regulatory reviews are underway in several
jurisdictions for ovarian, breast, pancreatic and prostate
cancers.
Lynparza, which is being
jointly developed and commercialised by AstraZeneca and MSD, has
been used to treat over 30,000 patients
worldwide. Lynparza has the broadest and most advanced clinical
trial development programme of any PARP inhibitor, and AstraZeneca
and MSD are working together to understand how it may affect
multiple PARP-dependent tumours as a monotherapy and in combination
across multiple cancer types. Lynparza is the foundation of AstraZeneca's
industry-leading portfolio of potential new medicines targeting DDR
mechanisms in cancer cells
The AstraZeneca and MSD strategic oncology
collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth,
NJ, US, known as MSD outside the US and Canada, announced a global
strategic oncology collaboration to co-develop and
co-commercialise Lynparza, the world's first PARP inhibitor,
and Koselugo (selumetinib), a MEK inhibitor, for multiple cancer types.
Working together, the companies will
develop Lynparza and Koselugo in combination with other potential new
medicines and as monotherapies. Independently, the companies will
develop Lynparza and Koselugo in combination with their respective PD-L1
and PD-1 medicines.
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 six new medicines
launched between 2014 and 2020, and a broad
pipeline of small molecules and biologics in development,
the Company is committed to advance oncology as a key growth driver
for AstraZeneca focused on lung, ovarian, breast and blood cancers.
In addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investment that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, Cardiovascular, Renal and Metabolism, and Respiratory and
Immunology. Based in Cambridge, UK, AstraZeneca operates
in over 100 countries and its innovative medicines are used by
millions of patients worldwide. Please
visit astrazeneca.com and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Cancer.org.
(2020). Ovarian Cancer Statistics | How Common Is Ovarian Cancer.
Available at: www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html. [Accessed
March 2020].
2. The World
Health Organization. IARC. Globocan 2018. Available
at: http://gco.iarc.fr/ [Accessed March 2020].
3. National Cancer
Institute. (2019). Cancer Stat Facts: Ovarian Cancer
Available at: https://seer.cancer.gov/statfacts/html/ovary.html [Accessed March 2020].
4. Moschetta et al. (2016). BRCA
somatic mutations and epigenetic BRCA modifications in serous
ovarian cancer. Annals of
Oncology, 27(8),
pp.1449-1455.
5. da Cunha Colombo Bonadio et al.
(2018). Homologous recombination deficiency in ovarian cancer: a
review of its epidemiology and management. Clinics (Sao
Paulo). 2018;73(suppl
1):e450s.
6. Moore, K. (2018). Maintenance
Olaparib in Patients with Newly Diagnosed Advanced Ovarian
Cancer. New England Journal of
Medicine, 379(26),
pp.2495-2505.
7. Raja et al. 2012. Optimal
first-line treatment in ovarian cancer. Annals on
Oncology. 23 Suppl 10,
x118-127.
8.
NHS Choices, Ovarian Cancer Available at:
https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed March 2020].
9. Ledermann et al. (2013). Newly
diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical
Practice Guidelines for diagnosis, treatment and
follow-up. Annals of
Oncology, 24,
pp.vi24-vi32.
10.
AstraZeneca data on file. Kantar Health, Q1 2020.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
11 May
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|