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 December
2019
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 a 1st-line maintenance
treatment of
germline BRCA-mutated metastatic pancreatic
cancer
30 December 2019 07:00 GMT
Lynparza approved in the US as a 1st-line maintenance
treatment
of germline BRCA-mutated metastatic pancreatic cancer
Lynparza reduced the risk of disease progression or death by 47% in
patients
whose disease had not progressed on at least 16 weeks of a 1st-line
platinum-based chemotherapy regimen
Only PARP inhibitor approved in germline BRCA-mutated
metastatic pancreatic cancer
AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck
& Co., Inc. inside the US and Canada) today announced
that Lynparza (olaparib) has been approved in the US for
the maintenance treatment of adult patients with deleterious or
suspected deleterious germline BRCA-mutated (gBRCAm) metastatic
pancreatic adenocarcinoma (pancreatic cancer) whose disease has not
progressed on at least 16 weeks of a 1st-line platinum-based
chemotherapy regimen. Patients will be selected for therapy based
on an FDA-approved companion diagnostic
for Lynparza.
The approval follows the recommendation from
the US FDA Oncologic Drugs Advisory Committee (ODAC) on 17 December
for Lynparza in this indication, and was based on results
from the pivotal Phase III POLO
trial published
in The
New England Journal of Medicine and
presented at the 2019 American Society of Clinical Oncology Annual
Meeting.
Results showed a statistically significant and clinically
meaningful improvement in progression-free survival,
where Lynparza nearly doubled the time patients with gBRCAm
metastatic pancreatic cancer lived without disease progression or
death to a median of 7.4 months vs. 3.8 months on placebo. The
safety and tolerability profile of Lynparza in
the POLO trial was in line with that observed in prior clinical
trials.
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "Patients with advanced pancreatic cancer historically have
faced poor outcomes due to the aggressive nature of the disease and
limited treatment advances over the last few
decades. Lynparza is now the only approved targeted medicine
in biomarker-selected patients with advanced pancreatic
cancer."
Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, MSD Research Laboratories,
said: "Lynparza embodies MSD's and AstraZeneca's commitment
to advance the treatment of challenging types of cancer, including
metastatic pancreatic cancer. The expanded approval
of Lynparza represents a significant milestone for
patients and supports the value of germline BRCA testing in
patients with this disease."
Hedy L. Kindler, Co-Principal Investigator of the POLO trial and
Professor of Medicine, University of Chicago Medicine, said:
"Today's approval of olaparib based on the POLO results gives
clinicians an important 1st-line maintenance treatment option which
nearly doubled the progression-free survival benefit in patients
with germline BRCA-mutated metastatic pancreatic
cancer."
Julie Fleshman, President and CEO, Pancreatic Cancer Action
Network, said: "Metastatic pancreatic cancer patients have been
waiting a long time for new therapy options for their devastating
disease. Today's approval of Lynparza provides an exciting new treatment option
for patients with germline BRCA-mutated metastatic pancreatic
cancer."
The Pancreatic Cancer
Action Network (PanCAN) is
a US-based organisation that supports and advocates on behalf of
the patients, caregivers and communities affected by pancreatic
cancer.
About pancreatic cancer
Pancreatic cancer is a deadly cancer with a high unmet medical
need. It is the 12th most commonly occurring
cancer2 and
the 7th leading cause of cancer death globally.3 The
disease has the lowest survival rate of the most common
cancers4,5 and
is the only major cancer with a single-digit five-year survival
rate (2-9%) in nearly every country.5 There
were approximately 460,000 new cases worldwide in
20186. As
there are often no symptoms, or symptoms may be non-specific in the
early stages7,
it is most commonly diagnosed at an incurable
stage.8 Around
80% of pancreatic cancer patients are diagnosed when the disease
has metastasised and for these the average survival is less than a
year.9 Despite
advances in treatment10,
few improvements have been made in diagnosis and treatment over the
decades.11,12 Current
treatment is surgery (for which approximately only 10-20% of
patients are eligible), chemotherapy and radiotherapy, highlighting
a critical unmet medical need for more effective treatment
options.13
About POLO
POLO is a Phase III randomised, double-blinded, placebo-controlled,
multi-centre trial of Lynparza tablets (300mg twice daily) as maintenance
monotherapy vs. placebo. The trial randomised 154 patients with
gBRCAm metastatic pancreatic cancer whose disease had not
progressed on 1st-line platinum-based chemotherapy. Patients were
randomised (3:2) to receive Lynparza or placebo until disease progression. The
primary endpoint was PFS and key secondary endpoints included
overall survival, time to second disease progression, overall
response rate and health-related quality of
life.1
The results showed a statistically significant and clinically
meaningful improvement in progression-free survival,
where Lynparza nearly doubled the time patients with gBRCAm
metastatic pancreatic cancer lived without disease progression or
death to a median of 7.4 months vs. 3.8 months on placebo and
reduced the risk of disease progression or death by 47% (HR 0.53
[95% CI, 0.35-0.81], p=0.0035). The benefit of maintenance
with Lynparza was seen consistently across a range of
clinically meaningful endpoints. In patients with measurable
disease at baseline, 23% responded to Lynparza vs.12% on placebo (odds ratio, 2.30; 95% CI,
0.89 to 6.76) and had a median duration of treatment in excess of
two years (24.9 months; 95% CI, 14.8 to could not be calculated) vs
3.7 months on placebo (95% CI, 2.1 to could not be calculated).
Overall survival (OS), a secondary endpoint, at interim analysis
was 18.9 months for Lynparza vs. 18.1 months for placebo but did not
reach statistical significance (HR=0.90;
p=0.68).
The
safety and tolerability profile of Lynparza in the POLO trial was in
line with that observed in prior clinical trials. The most common
adverse reactions (ARs) ≥10% were fatigue (60%), nausea
(45%), abdominal pain (34%), diarrhoea (29%), anaemia (27%),
decreased appetite (25%), constipation (23%), vomiting (20%), back
pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%),
dyspnoea (13%), nasopharyngitis (12%), neutropenia (12%), dysgeusia
(11%) and stomatitis (10%). Grade 3 or above ARs were anaemia
(11%), fatigue (5%), neutropenia (4%), decreased appetite (3%),
thrombocytopenia (3%), abdominal pain (2%), vomiting (1%) and
arthralgia (1%). ARs led to dose reduction in 23% of patients
on Lynparza while
6% of patients discontinued treatment.
Based
on the results of POLO, the National Comprehensive Cancer Network
(NCCN) guidelines were updated in July 2019 to recommend Lynparza as maintenance treatment
for gBRCAm pancreatic cancer.14
In the
US, eligible metastatic pancreatic cancer patients will be selected
for therapy based on the FDA-approved companion diagnostic,
BRACAnalysis CDx, a genetic test that detects the presence of
a BRCA1 or BRCA2 gene mutation. BRACAnalysis CDx is owned and
commercialised by Myriad Genetics, Inc.
About BRCA mutations
BRCA1 and BRCA2 (breast cancer
susceptibility genes 1/2) 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 pathway.
Lynparza is currently
approved in 65 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, 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 44 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 advanced ovarian cancer and metastatic breast cancer
and has been used in 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 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, 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 investments 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 (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.
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.
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References
1. Golan et al (2019). Maintenance Olaparib for Germline
BRCA-Mutated Metastatic Pancreatic Cancer. New England Journal of
Medicine.
2. World Cancer Research Fund
International. Pancreatic cancer statistics. Available
at: www.wcrf.org/dietandcancer/cancer-trends/pancreatic-cancer-statistics Accessed
October 2019.
3. World Health Organization. IARC.
(2019). Estimated number of deaths in 2018, worldwide, both sexes,
all ages. Website available here. Accessed
October 2019.
4. Pancreaticcancer.org.uk. Pancreatic
cancer statistics. Available at: www.pancreaticcancer.org.uk/statistics/ Accessed
October 2019.
5. Worldpancreaticcancerday.org.
Available at: www.worldpancreaticcancerday.org/about-pancreatic-cancer/ Accessed
October 2019.
6. World Health Organization. IARC.
(2019). Estimated number of new cases in 2018, worldwide, both
sexes, all ages. Website available here. Accessed
October 2019.
7. Pancreaticcancer.org.uk. Signs and
symptoms of pancreatic cancer. Available
at: www.pancreaticcancer.org.uk/information-and-support/facts-about-pancreatic-cancer/signs-and-symptoms-of-pancreatic-cancer/ Accessed
October 2019.
8. DaVee (2018). Pancreatic cancer
screening in high-risk individuals with germline genetic
mutations. Gastrointestinal
Endoscopy. 87(6),
pp.1443-1450.
9. Azar et al. (2019). Treatment and survival rates of
stage IV pancreatic cancer at VA hospitals: a nation-wide
study. Journal of Gastrointestinal
Oncology, 10(4),
pp.703-711.
10. Sheahan et al. (2018). Targeted therapies in the management of
locally advanced and metastatic pancreatic cancer: a systematic
review. Oncotarget. 9(30): 21613-21627.
11. Adamska et al. (2017). Pancreatic ductal adenocarcinoma:
current and evolving therapies. International Journal of
Molecular Science. 18(7):
1338.
12. Yongxing et al. (2017). Molecular subtyping of pancreatic
cancer: translating genomics and transcriptomics into the
clinic. Journal of
Cancer. 8(4):513-522.
13. Stunt, A. (2016). Pancreatic cancer: GPs
can help prognosis by identifying early signs. Guidelines in
Practice. Available at: www.guidelinesinpractice.co.uk/cancer/pancreatic-cancer-gps-can-help-prognosis-by-identifying-early-signs/352855.article Accessed
October 2019.
14. NCCN. (2019). NCCN Guidelines for
Patients | Pancreatic Cancer. Nccn.org. Available
at: https://www.nccn.org/patients/guidelines/pancreatic/12/ Accessed
December 2019.
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 December
2019
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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