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2017-08-17

AstraZeneca: Lynparza receives additional and broad approval in the US for ovarian cancer

Lynparza's new tablet formulation approved as maintenance treatment
for women with platinum-sensitive recurrent ovarian cancer regardless
of BRCA-mutation status

Lynparza tablets also indicated in BRCA-mutated ovarian cancer beyond
the third-line setting

Newly-approved tablet formulation means improved patient convenience

AstraZeneca and Merck & Co., Inc., (Merck: known as MSD outside the
U.S. and Canada) today announced that the US Food and Drug
Administration (FDA) has granted approval for the PARP inhibitor,
Lynparza (olaparib), as follows:

· New use of Lynparza as a maintenance treatment for recurrent,
epithelial ovarian, fallopian tube or primary peritoneal adult cancer
who are in response to platinum-based chemotherapy, regardless of
BRCA status;

· New use of Lynparza tablets (2 tablets twice daily) as opposed to
capsules (8 capsules twice daily);

· Lynparza tablets also now indicated (conversion from the current
accelerated approval
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2...))
for the use in patients with deleterious or suspected deleterious
germline BRCA-mutated advanced ovarian cancer, who have been treated
with three or more prior lines of chemotherapy.

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer, AstraZeneca, said: "Physicians have almost
three years of clinical experience with Lynparza on the market and we
are now pleased to bring this important medicine, in a new tablet
formulation, to a broader group of women. Today's approvals validate
more than 10 years of dedicated research behind Lynparza, the world's
first PARP inhibitor, which now provides oncologists with the greater
flexibility for use in terms of treatment settings. It builds on our
recently-announced collaboration with Merck, which aims to further
increase the number of treatment options available to patients."

Eric Pujade-Lauraine, Head of the Women Cancers and Clinical Research
Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu,
AP-HP and Principal Investigator of the SOLO-2 trial, one of the
trials supporting the approval, said: "Today's approval is welcome
news for US patients with ovarian cancer, who are now able to benefit
from treatment with olaparib irrespective of their BRCA-mutation
status. This latest regulatory milestone underscores the breadth and
depth of clinical data on olaparib, and not only demonstrates its
efficacy as maintenance therapy, but adds to the data presented
earlier this year showing sustained quality of life for patients
undergoing treatment for this serious disease."

Roger M. Perlmutter, President of Merck Research Laboratories, said:
"We congratulate AstraZeneca on the approval of these new indications
and the new dosage form and schedule for Lynparza, an important
therapeutic advance for many patients with ovarian cancer. This is a
significant first regulatory event in our collaboration with
AstraZeneca. We look forward to working with AstraZeneca in our
global collaboration to bring this medicine with its new indications
to patients."

Two randomised trials supported the new approvals and the conversion
of accelerated approval to full approval which was originally based
on a single-arm trial:

· SOLO-2 (n=295) confirmed the benefit of Lynparza in germline
BRCA-mutated (gBRCAm) patients, demonstrating a 70% reduced risk of
disease progression or death (HR 0.30 [95% CI, 0.22-0.41], P<0.0001)
and improved progression-free survival (PFS) to 19.1 vs 5.5 months
for placebo by investigator-assessed analysis.

· Study 19 (n=265) showed that Lynparza reduced the risk of disease
progression or death by 65% and improved PFS compared with placebo in
patients of any BRCA status (HR 0.35 [95% CI, 0.25-0.49], P<0.0001;
median PFS of 8.4 months vs 4.8 months for placebo). Additionally,
patients in Study 19, treated with Lynparza as a maintenance therapy,
had a median overall survival (OS) of 29.8 months vs 27.8 months for
placebo (HR 0.73 [95% CI, 0.55-0.95]).

Table 1. Summary of key efficacy results from randomised trials:

+--------+--------+----------------------------+-----------------+
|Analysis |Reduction in the risk of |Reduction in the |
| |disease progression or death|risk of death |
| |(PFS) |(OS) |
+--------+--------+----------------------------+-----------------+
|SOLO-2 |Lynparza|70% (HR 0.30 [95% CI, 0.22- |Data not yet |
|[gBRCAm]|Placebo |0.41], P<0.0001) |mature |
+--------+--------+----------------------------+-----------------+
| |
+--------+--------+----------------------------+-----------------+
|Study 19|Lynparza|65% (HR 0.35 [95% CI, 0.25- |27% (HR 0.73 [95%|
|[PSROC*]| Placebo|0.49], P<0.0001) |CI, 0.55-0.95] |
+--------+--------+----------------------------+-----------------+
| |
+--------+--------+----------------------------+-----------------+

*PSR = Platinum-sensitive recurrent ovarian cancer

The most-common adverse events reported in 20% or more of patients
across the SOLO-2 trial in the Lynparza arm were anaemia (44%),
nausea (76%), vomiting (37%), diarrhoea (33%), fatigue/asthenia
(66%), decreased appetite (22%), headache (25%), and dysgeusia (27%).
The most-common Grade 3 or 4 adverse events were anaemia (20%),
nausea (2.6%), vomiting (2.6%), diarrhoea (1.0%), fatigue/asthenia
(4.1%), and headache (0.5%). Discontinuation of Lynparza resulting
from adverse events was seen in 11% of patients. Dose interruptions
of Lynparza due to an adverse reaction of any grade was 45%. Dose
reductions of Lynparza due to an adverse reaction was 25%.

The most-common adverse events reported in 20% or more of patients
across the Study 19 trial in the Lynparza arm were anaemia (23%),
nausea (71%), vomiting (35%), diarrhoea (27%), fatigue (including
asthenia) (63%), decreased appetite (21%), and headache (21%). The
most-common Grade 3 or 4 adverse events were anaemia (7.4%), nausea
(2.2%), vomiting (2.2%), diarrhoea (2.2%), and fatigue (including
asthenia) (8.8%). Discontinuation of Lynparza resulting from adverse
events was seen in 4% of patients. Dose interruptions of Lynparza due
to an adverse reaction of any grade was 25%. Dose reductions of
Lynparza due to an adverse reaction was 15%.

The full data from the SOLO-2 trial can be found in the 25 July 2017
publication of The Lancet Oncology
(http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30469-2/fulltext).

Lynparza was first approved under the FDA's Accelerated Approval
programme in December 2014, as a capsule formulation, making it the
first poly ADP-ribose polymerase (PARP) inhibitor approved. Since
then, more than 3,000 advanced ovarian cancer patients have been
treated with Lynparza capsules in its approved indication.

About SOLO-2

SOLO-2 was a Phase III, randomised, double-blinded, multicentre trial
designed to determine the efficacy of Lynparza tablets as a
maintenance monotherapy compared with placebo, in patients with
platinum-sensitive, relapsed or recurrent gBRCA-mutated ovarian,
fallopian tube and primary peritoneal cancer. The trial, conducted in
collaboration with the European Network for Gynaecological
Oncological Trial Groups (ENGOT) and Groupe d'Investigateurs National
pour l'Etude des Cancers de l'Ovaire et du sein (GINECO), randomised
295 patients with documented germline BRCA1 or BRCA2 mutations who
had received at least 2 prior lines of platinum-based chemotherapy
and were in complete or partial response. Eligible patients were
randomised to receive 300mg Lynparza tablets twice daily or placebo
tablets twice daily.

About Study 19

Study 19 was a Phase II, randomised, double-blinded,
placebo-controlled, multicentre trial, which evaluated the efficacy
and safety of Lynparza compared with placebo in relapsed, high-grade
serous ovarian cancer patients, involving 82 sites across 16
countries. Patients received Lynparza maintenance monotherapy, at a
dose of 400mg per day or matching placebo. Treatment continued until
disease progression if toxicities were manageable.

About Lynparza
Lynparza is an innovative, first-in-class oral poly ADP-ribose
polymerase (PARP) inhibitor that may exploit tumour DNA damage
response (DDR) pathway deficiencies to preferentially kill cancer
cells. It is approved by regulatory authorities in the EU and US for
the treatment of women with BRCAm ovarian cancer.

Lynparza is the foundation of AstraZeneca's industry-leading portfolio
of potential new medicines targeting DDR mechanisms in cancer cells.
Lynparza tablets are currently being tested in combinations in a
range of tumour types including breast, prostate, and pancreatic
cancers.

About the AstraZeneca and Merck Strategic Oncology Collaboration

On 27 July 2017, AstraZeneca and Merck & Co., Inc., announced a global
strategic oncology collaboration to co-develop and co-commercialise
AstraZeneca's Lynparza, the world's first and leading PARP inhibitor,
and potential new medicine selumetinib, a MEK inhibitor, for multiple
cancer types. The collaboration is based on increasing evidence that
PARP and MEK inhibitors can be combined with PDL-1/PD-1 inhibitors
for a range of tumour types and is aimed at maximising the potential
of Lynparza to become the preferred backbone of combination
therapies. Working together, the companies will jointly develop
Lynparza and selumetinib in combination with other potential new
medicines and as a monotherapy. Independently, the companies will
develop Lynparza and selumetinib in combination with their respective
PD-L1 and PD-1 medicines.

About AstraZeneca in Ovarian Cancer
Worldwide, ovarian cancer is the 7th most-commonly diagnosed cancer
and the 8th most-common cause of cancer death in women. The risk of
developing ovarian cancer is increased in women with specific
inherited genetic abnormalities, including BRCA mutations.
AstraZeneca is committed to the continued development of our R&D
portfolio for ovarian cancer, with a focus on improved care for all
patients, including the development of targeted therapies for
patients with specific gene mutations such as BRCA.

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 New Oncology as one of AstraZeneca's five Growth
Platforms focused on lung, ovarian, breast and blood canc...

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