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 June
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
approved in the EU for 1st-line
18 June 2019 07:00 BST
Lynparza approved
in the EU for 1st-line maintenance
treatment of BRCA-mutated advanced ovarian cancer
60% of patients receiving Lynparza remained free of disease
progression
after three years vs. 27% on placebo in pivotal Phase III SOLO-1
trial
AstraZeneca and MSD's Lynparza is the only PARP
inhibitor approved in the EU for this indication
AstraZeneca
and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co.,
Inc. inside the US and Canada) today announced that the European
Commission (EC) has approved Lynparza(olaparib) as a 1st-line
maintenance treatment for women with BRCA-mutated advanced ovarian
cancer.
The
licensed indication is as a maintenance treatment of adult patients
with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline
and/or somatic) 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.
Dave
Fredrickson, Executive Vice President, Oncology Business Unit,
said: "This approval sets the stage for a new standard of care in
the EU for women with ovarian cancer and a BRCA mutation. The goals
of front-line therapy have always been long-term remission and even
cure, yet currently 70% of patients relapse within three years of
initial treatment. The progression-free survival benefit
of Lynparza observed in SOLO-1
represents a major step forward in our ambition to help transform
patient outcomes."
Roy
Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "In SOLO-1, Lynparza demonstrated
clinically-meaningful results with a 70% reduction in the risk of
disease progression or death in the first-line maintenance
treatment of patients with BRCAm advanced ovarian cancer.
Merck and AstraZeneca are committed to improving outcomes for
people with cancer and we will work to bring this new option
to women in the EU, many of whom have historically poor outcomes,
as quickly as possible."
The EC
approval was based on data from the pivotal Phase III
SOLO-1 trial which tested Lynparza as maintenance
monotherapy compared with placebo in patients with BRCAm advanced
ovarian cancer following 1st-line platinum-based chemotherapy.
Results announced in
October 2018 at 40.7 months of follow-up showed the median time of
progression for patients treated with Lynparza had not yet been reached
vs. 13.8 months for those on placebo (HR 0.30 [95% CI, 0.23-0.41],
p<0.001).
This is the third indication for Lynparza in the EU. AstraZeneca and MSD are exploring
additional trials in ovarian cancer, including the ongoing Phase
III PAOLA-1 trial, which is testing Lynparza in combination with bevacizumab as a
1st-line maintenance treatment for women with newly-diagnosed,
advanced, stage IIIB-IV high grade serous or endometrioid ovarian
cancer, regardless of BRCA status.
About SOLO-1
SOLO-1 was a Phase III, randomised, double-blinded,
placebo-controlled, multi-centre trial to evaluate the efficacy and
safety of Lynparza tablets (300mg twice daily) as a maintenance
monotherapy compared with placebo in patients with BRCAm advanced
ovarian cancer following first-line platinum-based chemotherapy.
The trial randomised 391 patients with a deleterious or suspected
deleterious germline or somatic BRCA1 or BRCA2 mutation who were in
clinical complete or partial response following platinum-based
chemotherapy.
Patients were randomised (2:1) to receive Lynparza or placebo for up to two years or until
disease progression. Patients who had a partial response at two
years were permitted to stay on therapy at the investigator's discretion. The
primary endpoint was progression-free survival (PFS) and key
secondary endpoints included time to second disease progression or
death, time to first subsequent treatment and overall
survival.
The data were presented on 21 October 2018, at the Presidential
Symposium of the ESMO (European Society for Medical Oncology) 2018
Congress in Munich, Germany and published simultaneously
online in The
New England Journal of Medicine.
Summary of PFSi,ii
|
Lynparza (n=260)
|
Placebo
(n=131)
|
Number
of patients with event (%)iii
|
102
(39)
|
96
(73)
|
Median
PFS (in months)
|
Not
reached
|
13.8
|
Hazard
ratio (95% CI)
|
0.30
(0.23-0.41)
|
P-value
|
p<0.001
|
i Investigator-assessed.
ii Median (interquartile range) duration of follow-up 40.7 months
(34.9-42.9) for Lynparza and
41.2 months (32.2-41.6) for placebo.
iii Analysis was done at 50.6% maturity.
The SOLO-1 safety profile was in line with that observed in prior
clinical trials. The most common adverse events (AEs) ≥ 20%
were nausea (77%), fatigue (63%), vomiting (40%), anaemia (39%) and
diarrhoea (34%). The most common ≥ Grade 3 AEs were anaemia
(22%) and neutropenia (9%). Some 71% of patients
on Lynparza remained on the recommended starting dose.
Additionally, 88% of patients on Lynparza continued treatment without an AE-related
discontinuation.
Financial considerations
Under the oncology collaboration with MSD and following this new
approval for Lynparza, AstraZeneca will receive $30m as Ongoing
Collaboration Revenue, anticipated to be booked by the Company
during the second quarter of 2019.
About ovarian cancer
Ovarian cancer is a leading cause of cancer deaths in women
worldwide, with a five-year survival rate of
19%.1 In
2018, there were nearly 300,000 new cases diagnosed and around
185,000 deaths.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 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
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.
Lynparza is currently approved in over 60 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, Canada, Brazil and now the EU as
1st-line maintenance treatment of BRCAm advanced ovarian cancer
following response to platinum-based chemotherapy. It is also
approved in nearly 40 countries for germline BRCAm HER2-negative
metastatic breast cancer previously treated with chemotherapy.
Regulatory reviews are underway in other jurisdictions for both
ovarian cancer and breast cancer.
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 the AstraZeneca and MSD 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-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, 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
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 & Metabolism and
Respiratory. AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients
worldwide. For more information,
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
|
BioPharma
|
+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
|
Investor
Relations
|
|
|
Thomas
Kudsk Larsen
|
|
+44 203
749 5712
|
Henry
Wheeler
|
Oncology
|
+44 203
749 5797
|
Christer
Gruvris
|
BioPharma
(cardiovascular, metabolism)
|
+44 203
749 5711
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Nick
Stone
|
BioPharma
(respiratory, renal)
|
+44 203
749 5716
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Josie
Afolabi
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Other
medicines
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+44 203
749 5631
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Craig
Marks
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Finance,
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+44
7881 615 764
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Kretzmann
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Corporate
access, retail investors
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+44 203
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US
toll-free
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+1 866
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Adrian Kemp
Company Secretary
AstraZeneca PLC
References
1. American Cancer Society. Survival Rates for Ovarian Cancer, by
Stage. Available at: https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Accessed:
March 2019.
2. Globocan 2018 http://gco.iarc.fr/.
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. Optimal
first-line treatment in ovarian cancer. Ann. Oncol. Off. J. Eur.
Soc. Med. Oncol. 23 Suppl 10, x118-127 (2012).
5. NHS Choices, Ovarian Cancer Accessed https://www.nhs.uk/conditions/ovarian-cancer/treatment/ in
September 2018.
6.
Ledermann.et al. 2013. Newly diagnosed and relapsed epithelial
ovarian carcinoma: ESMO Clinical Practice.
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:
18 June
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|