Blueprint
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
2019
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 improved
the time women lived without disease progression to 22 months in
the broad population and to 37 months in HRD-positive
patients as 1st-line maintenance treatment with
bevacizumab for newly-diagnosed advanced ovarian
cancer
30 September 2019 07:00 BST
Lynparza improved the time women lived without
disease progression to 22 months in the broad population and to 37
months in HRD-positive patients as 1st-line maintenance
treatment with bevacizumab for newly-diagnosed advanced
ovarian cancer
AstraZeneca and MSD's Lynparza added to bevacizumab reduced the
risk of disease progression or death by 41% in the overall trial
population
AstraZeneca
and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co.,
Inc. inside the US and Canada) today announced detailed positive
results from the Phase III PAOLA-1 trial, showing Lynparza(olaparib) demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival (PFS) in women with newly-diagnosed
advanced ovarian cancer.
The
trial compared Lynparza when added to
standard-of-care (SoC) bevacizumab vs. bevacizumab alone in women
in the 1st-line maintenance setting, irrespective of their genetic
biomarker status or outcome from previous surgery.
Investigator-assessed results showed Lynparza added to bevacizumab
reduced the risk of disease progression or death by 41% (equal to a
hazard ratio of 0.59) and improved PFS to a median of 22.1 months
vs. 16.6 months for those treated with bevacizumab alone. At two
years since trial initiation, 46% of women treated
with Lynparza added to bevacizumab
showed no disease progression vs. 28% of women receiving
bevacizumab alone.
The
sensitivity analysis of blinded independent central review (BICR)
of PFS was consistent, showing a
similar improvement with a median of 26.1 months
for Lynparza added to
bevacizumab vs. 18.3 months for bevacizumab alone. The safety and
tolerability profile of Lynparza and bevacizumab were
consistent with those known from previous trials for each medicine,
and with no detriment to quality of life.
The
results were presented during the Presidential Symposium of the
2019 European Society of Medical Oncology (ESMO) congress in
Barcelona, Spain (Abstract #LBA2_PR).
The
trial also included exploratory sub-group analyses including
BRCA-mutated (BRCAm) and broader homologous recombination
deficiency (HRD) populations, which showed treatment
with Lynparza added to bevacizumab
demonstrated greater benefit vs. bevacizumab alone. In the
BRCAm-positive sub-group, Lynparza added to bevacizumab
reduced the risk of disease progression or death by 69% (equal to a
hazard ratio of 0.31). In the broader HRD-positive sub-group, which
represents approximately half of women with newly-diagnosed
advanced ovarian cancer and includes BRCAm, Lynparza added to
bevacizumab reduced the risk of disease progression or death by 67%
(equal to a hazard ratio of 0.33).
José
Baselga, Executive Vice President, Oncology R&D, said: "This
trial was designed to reflect everyday clinical practice using a
global standard-of-care treatment with Lynparza. The results showed at
two years nearly half of women with advanced ovarian cancer were
progression-free with Lynparza added to bevacizumab as a
1st-line maintenance treatment, regardless of their biomarker
status or surgical outcome. We are working with regulatory
authorities to bring Lynparza to these patients as
quickly as possible."
Roy
Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "PAOLA-1 is the second positive Phase III trial
involving Lynparza in the 1st-line
maintenance setting for advanced ovarian cancer. Following the
positive SOLO-1 trial, we are encouraged by the PAOLA-1 results
which reaffirm AstraZeneca and MSD's ongoing commitment to explore
potential treatment options for more women with ovarian
cancer."
Isabelle
Ray-Coquard, principal investigator of the PAOLA-1 trial and
medical oncologist, Centre Léon Bérard and President of
the GINECO group, said: "The goal of 1st-line, including
maintenance, treatment for women with newly-diagnosed advanced
ovarian cancer is to delay relapse. Unfortunately, the risk of
relapsing is high, as two out of three women relapse within three
years of initial diagnosis. In PAOLA-1, the results
of Lynparza added to
bevacizumab were significant and have the potential to change
clinical practice in how women with advanced ovarian cancer are
treated in the 1st-line maintenance setting."
Summary of PFS in overall population
|
Median in months
|
Hazard Ratio (95% CI)
|
|
Lynparza +
bevacizumab
|
bevacizumab alone
|
|
PFS (investigator assessed)
(n=806)
|
22.1
|
16.6
|
0.59 (0.49-0.72)
p<0.0001
|
PFS (BICR)
|
26.1
|
18.3
|
0.63 (0.51-0.77)
p<0.0001
|
Summary of PFS in exploratory subgroup analyses
|
Median in months
|
Hazard Ratio (95% CI)
|
|
Lynparza +
bevacizumab
|
bevacizumab alone
|
|
PFS by BRCAm status
|
BRCAm
(n=237)
|
37.2 i
|
21.7
|
0.31 (0.20-0.47)
|
Non-BRCAm
(n=569)
|
18.9
|
16.0
|
0.71 (0.58-0.88)
|
PFS by HRD status
|
HRD-positive
(n=387)
|
37.2 i
|
17.7
|
0.33 (0.25-0.45)
|
HRD-positive,
non-BRCAm (n=152)
|
28.1 i
|
16.6
|
0.43 (0.28-0.66)
|
HRD-negative/unknown
(n=419)
|
16.9
|
16.0
|
0.92
(0.72-1.17)
|
i The median PFS estimate
is immature at this time (below 50% maturity) and will evolve with
additional follow up
Overall
Grade 3 or above adverse events (AEs) were 57%
for Lynparza added to bevacizumab and 51% for bevacizumab
alone. The most common AEs ≥20% were nausea (53%),
fatigue (53%), hypertension (46%), anaemia (41%), lymphopenia
(24%), vomiting (22%) and arthralgia (22%). Grade 3 or above AEs
were hypertension (19%), anaemia (17%), lymphopenia (7%),
neutropenia (6%), fatigue (5%), nausea (2%), diarrhoea (2%),
leukopenia (2%) vomiting (1%) and abdominal pain (1%). AEs led to
dose interruption in 54% of patients on Lynparza while
20% of patients discontinued treatment.
Lynparza, which is being jointly developed and
commercialised by AstraZeneca and MSD, is approved for the
treatment of advanced ovarian cancer and metastatic breast cancer
and has been used to treat over 25,000 patients worldwide. It is
the only PARP inhibitor with positive Phase III trials in four
different cancer types (ovarian, breast, pancreatic and
prostate).
About PAOLA-1
PAOLA-1
is a double-blind Phase III trial testing the efficacy and safety
of Lynparza added
to SoC 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.
PAOLA-1
is an ENGOT (European Network of Gynaecological Oncological Trial
groups) trial, sponsored by ARCAGY Research (Association de
Recherche sur les CAncers dont GYnécologiques) on behalf of
GINECO (Groupe d'Investigateurs National des Etudes des Cancers
Ovariens et du sein). ARCAGY-GINECO is an academic group
specialising in clinical and translational research in patients'
cancers and a member of the GCIG (Gynecologic Cancer
InterGroup).
About ovarian cancer
Ovarian cancer is the eighth most common cause of death from cancer
in women worldwide. In 2018, there were nearly 300,000 new cases
diagnosed and around 185,000 deaths.1 Most women are diagnosed with advanced (Stage III
or IV) ovarian cancer and have a five-year survival rate of
approximately 30%.2 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.3,4,5,6
About homologous recombination deficiency
Homologous recombination deficiencies (HRDs) encompass a wide range
of genetic abnormalities, including BRCA mutations, that can be
detected using tests. As the BRCA gene drives DNA repair via
homologous recombination, mutation of this gene leads to HR
deficiency thereby interfering with normal cell DNA
repair mechanisms. BRCA mutations
are just one of many HRDs which are found in up to half of all
newly diagnosed advanced ovarian cancer patients and confer
sensitivity to PARP inhibitors including Lynparza.
About Lynparza
Lynparza 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 64 countries,
including those in the EU, for the maintenance treatment of
platinum-sensitive relapsed ovarian cancer, regardless of BRCA
status. It is approved in the US, the EU, Japan 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 43 countries, including the US
and Japan, for germline BRCA-mutated, HER2-negative, metastatic
breast cancer, previously treated with chemotherapy; in the EU,
this includes locally-advanced breast cancer. Regulatory reviews
are underway in other jurisdictions for ovarian, breast and
pancreatic cancers.
Lynparza, which is being jointly developed and
commercialised by AstraZeneca and MSD, is approved for the
treatment of advanced ovarian cancer and metastatic breast cancer
and has been used to treat over 25,000 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.
About GINECO
GINECO
(Groupe d'Investigateurs National des Etudes des Cancers Ovariens
et du sein) is the French Cooperative Group in Oncology labelled by
INCA (Institut National du Cancer, or French NCI) developing and
conducting gynaecological and metastatic breast cancer clinical
trials at the national and international level. Founded in 1993,
the GINECO group is a member of international consortia such as
ENGOT and GCIG.
About ENGOT
ENGOT
(European Network for Gynaecological Oncological Trial groups) is a
research network of the European Society of Gynaecological Oncology
(ESGO). Founded in 2007, ENGOT includes 21 cooperative groups from
25 European countries.
About GCIG
The
GCIG (Gynecological Cancer InterGroup) aims to promote and
facilitate high quality clinical trials in order to improve
outcomes for women with gynaecological cancer. Founded in 1998,
GCIG includes 23 cooperative groups from 28 countries
worldwide.
About 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 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.
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, 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.
About AstraZeneca
AstraZeneca 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 (CVRM), and Respiratory. AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and
follow us on Twitter @AstraZeneca.
Media Relations
|
|
|
Gonzalo
Viña
|
|
+44 203 749 5916
|
Rob
Skelding
|
Oncology
|
+44 203 749 5821
|
Rebecca
Einhorn
|
Oncology
|
+1 301 518 4122
|
Matt
Kent
|
BioPharmaceuticals
|
+44 203 749 5906
|
Jennifer
Hursit
|
Other
|
+44 203 749 5762
|
Christina
Malmberg Hägerstrand
|
Sweden
|
+46 8 552 53 106
|
Michele
Meixell
|
US
|
+1 302 885 2677
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Investor Relations
|
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Thomas
Kudsk Larsen
|
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+44 203 749 5712
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Henry
Wheeler
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Oncology
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+44 203 749 5797
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Christer
Gruvris
|
BioPharmaceuticals (CV, metabolism)
|
+44 203 749 5711
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Nick
Stone
|
BioPharmaceuticals (respiratory, renal)
|
+44 203 749 5716
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Josie
Afolabi
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Other medicines
|
+44 203 749 5631
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Craig
Marks
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Finance, fixed income
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+44 7881 615 764
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Jennifer
Kretzmann
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Corporate access, retail investors
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+44 203 749 5824
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US
toll-free
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+1 866 381 72 77
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References
1. The World Health Organization. IARC. Globocan 2018. Available
at: http://gco.iarc.fr/. [Accessed
August 2019].
2. National Cancer Institute. (2019). Cancer Stat Facts: Ovarian
Cancer Available at:https://seer.cancer.gov/statfacts/html/ovary.html [Accessed
August 2019].
3. Moore K et al. Maintenance Olaparib in Patients with Newly
Diagnosed Advanced Ovarian Cancer. Presented at
ESMO October 2018.
4. Raja, F. A., Chopra, N. & Ledermann, J. A. 2012. Optimal
first-line treatment in ovarian cancer. Ann. Oncol. Off. J. Eur.
Soc. Med. Oncol. 23 Suppl 10, x118-127.
5. NHS Choices, Ovarian Cancer Available
at: https://www.nhs.uk/conditions/ovarian-cancer/treatment/ [Accessed
August 2019].
6. Ledermann.et al. 2013. Newly diagnosed and relapsed epithelial
ovarian carcinoma: ESMO Clinical Practice for diagnosis, treatment
and follow-up. Annals of
Oncology, 24(suppl 6),
pp.vi24-vi32.
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:
30 September
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|