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2020-01-13

AstraZeneca: Lynparza regulatory submission granted Priority Review in the US for 1st-line maintenance treatment with bevac...

Submission based on Phase III PAOLA-1 trial for patients with advanced
ovarian cancer regardless of biomarker status or surgical outcome

AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck &
Co., Inc. inside the US and Canada) today announced that a
supplemental New Drug Application for Lynparza (olaparib) in
combination with bevacizumab has been accepted and granted Priority
Review in the US for the maintenance treatment of patients with
advanced ovarian cancer who are in complete or partial response to
1st-line platinum-based chemotherapy with bevacizumab.

A Prescription Drug User Fee Act (PDUFA) date is set for the second
quarter of 2020.

The Priority Review by the US Food and Drug Administration (FDA) was
based on results from the pivotal Phase III PAOLA-1 trial, which were
published in The New England Journal of Medicine
(https://www.nejm.org/doi/full/10.1056/NEJMoa1911361). The trial
compared Lynparza when added to standard-of-care (SoC) bevacizumab
vs. bevacizumab alone in patients with advanced ovarian cancer in the
1st-line maintenance setting, regardless of their biomarker status or
outcome from previous surgery.

The investigator-assessed results showed Lynparza added to bevacizumab
reduced the risk of disease progression or death by 41% based on a
hazard ratio of 0.59 (p<0.0001) and improved progression-free
survival (PFS) to a median of 22.1 months vs. 16.6 months for
patients treated with bevacizumab alone.

At two years after trial initiation, 46% of patients treated with
Lynparza added to bevacizumab showed no disease progression vs. 28%
of patients treated with bevacizumab alone. The safety and
tolerability profiles of Lynparza and bevacizumab were consistent
with previous trials for each medicine and showed no detriment to
quality of life.

Lynparza is the only PARP inhibitor with two positive randomised Phase
III trials in the 1st-line maintenance setting for advanced ovarian
cancer. It is the only PARP inhibitor approved in the US
(https://www.astrazeneca.com/media-centre/press-releases/2018/lynparza-ap...)
as a 1st-line maintenance treatment for patients with BRCA-mutated
advanced ovarian cancer, based on the SOLO-1 trial. If approved, this
would be the fourth indication for ovarian cancer patients in the US
for Lynparza.

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]

PAOLA-1

PAOLA-1 is a double-blind Phase III trial testing the efficacy and
safety of Lynparza added to standard-of-care 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.

Results showed Lynparza added to bevacizumab demonstrated a
statistically significant and clinically meaningful improvement in
PFS, reducing the risk of disease progression or death by 41% and
improving PFS to a median of 22.1 months versus 16.6 months for those
treated with bevacizumab alone (HR 0.59 [95% CI, 0.49-0.72],
p<0.0001). 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 (HR 0.63 [95% CI, 0.51-0.77],
p<0.0001).

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
added to bevacizumab while 20% of patients discontinued treatment.

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).

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 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. It is approved in the US as a 1st-line maintenance
treatment for germline BRCA-mutated metastatic pancreatic 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, metastatic breast cancer and metastatic pancreatic
cancer and 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 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.

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.

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
(http://www.astrazeneca.com/) and follow the Company on Twitter
@AstraZeneca (https://twitter.com/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 Sweden +46 8 552 53 106
Malmberg
Hägerstrand
Michele Meixell US +1 302 885 2677

Investor
Relations
Thomas Kudsk +44 203 749 5712
Larsen
Henry Wheeler Oncology +44 203 749 5797
Christer BioPharmaceuticals +44 203 749 5711
Gruvris (Cardiovascular, Metabolism)
Nick Stone BioPharmaceuticals (Renal) +44 203 749 5716
Environmental, Social and
Governance
Josie Afolabi BioPharmaceuticals +44 203 749 5631
(Respiratory) Other medicines
Craig Marks Finance Fixed in...

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