AstraZeneca PLC Announces FDA Advisory Committee Votes on Accelerated Approval for Investigational Medicine Olaparib


AstraZeneca today announced that the US Food and Drug Administration (FDA)
Oncologic Drugs Advisory Committee (ODAC) voted 11 to 2 that current evidence
from clinical studies does not support an accelerated approval for use of
olaparib as a maintenance treatment for women with platinum-sensitive relapsed
ovarian cancer who have the germline BRCA (gBRCA) mutation, and who are in
complete or partial response to platinum-based chemotherapy.

The ODAC provides the FDA with independent, expert advice and recommendations,
however the final decision regarding approval is made by the FDA.

AstraZeneca filed the US regulatory submission for olaparib in February 2014.
The FDA granted priority review status for the NDA in April and set a
Prescription Drug User Fee Act (PDUFA) action date of 3 October 2014.

Briggs Morrison, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca said: "Patients with germline BRCA-mutated
serous ovarian cancer have few options available to treat this disease. We are
disappointed with today's recommendation, and strongly believe that olaparib has
the potential to provide patients with relapsed BRCA-mutated ovarian cancer and
their doctors with a much-needed treatment option.  We look forward to
continuing to work with the FDA as it evaluates the Advisory Committee
recommendation and completes its review of the application. In the meantime, we
are continuing with our Phase III clinical programme to evaluate the benefit of
olaparib for this patient population. We aim to have completed this study by the
end of 2015."

The NDA filing was based on a subgroup analysis of Phase II data recently
published in Lancet Oncology1. The Phase II study was a randomised, double
-blind, placebo-controlled trial which evaluated olaparib versus placebo as
maintenance treatment in platinum-sensitive relapsed serous ovarian cancer
patients who had received previous treatment with at least two platinum regimens
and were in a maintained partial or complete response following their last
platinum regimen. The study met its primary endpoint of progression-free
survival by Response Evaluation Criteria in Solid Tumours guidelines. A pre
-defined subgroup analysis was conducted in patients who have germline BRCA
mutations.

In addition, as part of its commitment to bring the potential benefits of
olaparib to ovarian cancer patients, AstraZeneca has initiated and is committed
to complete the Phase III SOLO programme (http://www.astrazeneca.com/Media/Press
-releases/Article/astrazeneca-enrollment-patient-phaseIII-olaparib), designed to
evaluate the efficacy and safety of olaparib as a maintenance monotherapy in
ovarian cancer patients who have a BRCA mutation who are in complete or partial
response following platinum-based chemotherapy in the relapsed setting.

1 Ledermann JA, et al. Olaparib maintenance therapy in patients with platinum
-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis
of outcomes by BRCA status in a randomised Phase II study. The Lancet Oncology
2014. http://dx.doi.org/10.1016/S1470-2045(14)70228-1.

About olaparib

Olaparib is an innovative, investigational, potential first-in-class oral poly
ADP ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway
deficiencies to selectively induce cancer cell death. This mode of action gives
olaparib the potential for activity in a range of tumour types with DNA repair
deficiencies.

PARP is a key enzyme in one of the DNA repair pathways in human cells.
Inhibition of PARP results in a build-up of DNA damage in the cell, requiring
repair via an alternative pathway called Homologous Recombination repair (HR).
Cancer cells that already have a HR pathway deficiency (HRD) are limited in
their ability to repair their DNA, overloading them with DNA damage and causing
them to die. A number of abnormalities can cause HRD in cancer cells including
BRCA gene mutations. HRD is associated with a range of tumor types, in
particular with breast and ovarian cancers.

In addition to ovarian cancer, olaparib is being investigated in combination
with chemotherapy in second-line gastric cancer in the GOLD study, while Phase
III studies evaluating olaparib in adjuvant and metastatic breast cancer with
BRCA mutations have recently been initiated.

About ovarian cancer

Ovarian cancer is the eighth most commonly diagnosed cancer in women and the
seventh leading cause of cancer death among women worldwide, mainly because it
is often diagnosed late and has an extremely poor prognosis. For the 75% of
ovarian cancer patients whose cancer has spread by the time of diagnosis, the
five-year survival rate is less than 50%, so there is a real need for additional
therapies beyond current standard of care, which is platinum-based
chemotherapy.

Women with BRCA1 or BRCA2 mutations have an increased risk of developing ovarian
cancer, and the course of their disease is similar to that of the overall
patient population. Up to 40% of patients with platinum-sensitive relapsed
ovarian cancer harbour a BRCA mutation, which is the most common cause of HRD.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialization of prescription
medicines, primarily for the treatment of cardiovascular, metabolic,
respiratory, inflammation, autoimmune, oncology, infection and neuroscience
diseases. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit: www.astrazeneca.com

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26 June 2014

- ENDS -

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