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 September 2020
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Lynparza recommended for
approval in EU by CHMP as 1st-line maintenance treatment with
bevacizumab for HRD-positive advanced ovarian
cancer
21 September 2020 07:00 BST
Lynparza recommended for approval in EU by CHMP as
1st-line maintenance treatment with bevacizumab for HRD-positive
advanced ovarian cancer
Patients treated with Lynparza and bevacizumab lived without
disease
progression for a median of 37.2 months vs. 17.7 months for
bevacizumab alone
One in two women with advanced ovarian cancer has an HRD-positive
tumour
AstraZeneca and MSD's Lynparza (olaparib) has been recommended for
marketing authorisation in the European Union (EU) for the 1st-line
maintenance treatment with bevacizumab of patients with homologous
recombination deficient (HRD)-positive advanced ovarian
cancer.
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency based its positive opinion on a biomarker
subgroup analysis of the PAOLA-1
Phase III trial, which was
published in The
New England Journal of Medicine.
The trial showed that Lynparza in combination with bevacizumab maintenance
treatment reduced the risk of disease progression or death by 67%
(based on a hazard ratio of 0.33; 95% confidence interval
0.25-0.45). 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.
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.1-3
Ovarian cancer is the fifth most common cause of cancer death in
Europe and the five-year survival rate is approximately 45%, due in
part because women are often diagnosed with advanced disease (Stage
III or IV).4,5
José Baselga, Executive Vice President, Oncology R&D,
said: "Half of all newly diagnosed patients with advanced ovarian
cancer have HRD-positive tumours. Lynparza together with bevacizumab has demonstrated a
median progression-free survival benefit of more than three years,
offering new hope for women in this setting. This recommendation is
a vital step toward addressing a significant unmet need and could
bring a new treatment option that delays relapse in this
devastating disease."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "HRD is an important biomarker of advanced ovarian cancer
that can inform how physicians in the EU treat this aggressive type
of cancer. This recommendation and the results from the
PAOLA-1 trial underscore the importance of HRD testing at diagnosis
to determine the best course of treatment for women with advanced
ovarian cancer."
The CHMP recommendation is for Lynparza in combination with bevacizumab for the
maintenance treatment of adult patients with advanced (FIGO stages
III and IV) high-grade epithelial ovarian, fallopian tube or
primary peritoneal cancer who are in response (complete or partial)
following completion of 1st-line platinum-based chemotherapy in
combination with bevacizumab and whose cancer is associated with
HRD positive status defined by either a breast cancer
susceptibility gene 1/2 (BRCA1/2) mutation and/or genomic
instability.
Further results from the PAOLA-1 trial recently presented
during the 2020 European Society for Medical Oncology virtual
congress showed that Lynparza in combination with bevacizumab maintenance
treatment demonstrated a statistically significant improvement in
the time to second disease progression (PFS2) versus bevacizumab
alone in patients with HRD-positive advanced ovarian cancer, a key
secondary endpoint. The results showed Lynparza with bevacizumab provided benefit beyond
first disease progression, improving PFS2 to a median of 50.3
months versus 35.3 months with bevacizumab
alone.
Lynparza in combination
with bevacizumab is approved in the
US and several other
countries as a 1st-line maintenance treatment for patients with
HRD-positive advanced ovarian cancer and is currently under
regulatory review in other countries around the
world.
Ovarian cancer
In 2018, there were nearly 68,000 new cases of ovarian cancer
diagnosed in Europe and around 45,000 deaths.4 Approximately
50% of ovarian cancers are HRD-positive including BRCA1/2
mutation.6,7 Approximately
22% of ovarian cancers have a BRCA1/2 mutation.6-8
Homologous recombination deficiency
HRD, which defines a subgroup 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.9
PAOLA-1
PAOLA-1 is a double-blind Phase III trial testing the efficacy and
safety of Lynparza added to standard-of-care bevacizumab
versus 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 in the overall trial
population.
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 (HRR), 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 as a 1st-line
maintenance treatment with bevacizumab for patients with
HRD-positive advanced ovarian cancer (BRCAm and/or genomic
instability). Lynparza is 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. It is also
approved in the US and several other countries for the treatment of
germline BRCAm metastatic pancreatic
cancer. Lynparza is approved in the US for HRR gene-mutated
mCRPC (BRCAm and other HRR gene mutations). Regulatory reviews are
underway in several countries 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 mitogen-activated protein
kinase (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 seven 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.
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 & Metabolism, and Respiratory
& 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. Raja et al. (2012). Optimal first-line treatment in ovarian
cancer. Annals on
Oncology. 23 Suppl 10,
x118-127.
2. NHS Choices, Ovarian Cancer Available
at: https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed September 2020].
3. 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.
4. The World Health Organization. IARC. Globocan. (2018). Available
at: http://gco.iarc.fr/ [Accessed
September 2020].
5. EuroHealth. (2018). Ovarian Cancer: The Silent Killer. Available
at: https://eurohealth.ie/policy-brief-women-and-ovarian-cancer-in-the-eu-2018/ [Accessed September 2020].
6. Moschetta et al. (2016). BRCA somatic mutations and epigenetic
BRCA modifications in serous ovarian
cancer. Annals of
Oncology, 27(8),
pp.1449-1455.
7. Bonadio et al. (2018). Homologous recombination deficiency in
ovarian cancer: a review of its epidemiology and
management. Clinics, 73(Suppl 1): e450s.
8. Pothuri. (2013). BRCA1- and BRCA2-related mutations: therapeutic
implications in ovarian cancer. Annals of
Oncology,
24.
9. Moore, K. (2018). Maintenance Olaparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. New England Journal of
Medicine, 379(26),
pp.2495-2505.
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:
21
September
2020
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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