LESINURAD APPROVED BY US FDA FOR GOUT

ZURAMPIC® (LESINURAD) APPROVED BY US FDA
FOR PATIENTS WITH GOUT

AstraZeneca (http://www.astrazeneca-us.com/) today announced that the US Food
and Drug Administration (FDA) has approved ZURAMPIC® (lesinurad) 200mg tablets
in combination with a xanthine oxidase inhibitor (XOI) for the treatment of
hyperuricemia associated with gout in patients who have not achieved target
serum uric acid (sUA) levels with an XOI alone.

ZURAMPIC inhibits the urate transporter, URAT1, which is responsible for the
majority of the renal reabsorption of uric acid. By inhibiting URAT1, ZURAMPIC
increases uric acid excretion and thereby lowers sUA.



In combination with the current standard of care, XOIs allopurinol or
febuxostat, ZURAMPIC provides a dual mechanism of action to increase excretion
and decrease production of uric acid, enabling more patients with inadequately
controlled gout to achieve target treatment goals.



Sean Bohen, Executive Vice President of Global Medicines Development and Chief
Medical Officer, AstraZeneca, said: "With the FDA approval of ZURAMPIC, we are
pleased to offer a new treatment option for the many patients who are suffering
from the effects of gout and who are not reaching the recommended serum uric
acid treatment targets with the current standard of care."



The FDA approval is based on data from three pivotal Phase III studies, CLEAR1,
CLEAR2 and CRYSTAL, which represent the largest clinical trial data set of gout
patients (n=1,537 total) treated with combination urate lowering therapy.

Gout is a serious and debilitating form of inflammatory arthritis caused by
hyperuricemia (elevated sUA). It affects millions of people around the globe,
many of whom do not reach recommended sUA treatment goals on XOIs, which
decrease production of uric acid.  For those inadequately controlled patients,
the addition of a urate-lowering therapy to increase excretion of uric acid may
help them achieve treatment goals.

Dr. Lawrence Edwards, Chairman and Chief Executive Officer of the Gout and Uric
Acid Education Society (GUAES), said: "A new approach to treating gout is long
overdue given there has been limited therapy innovation over the last 50 years.
Combination therapy with ZURAMPIC is an important addition to the medicines
available to physicians that will help more gout patients reach their serum uric
acid treatment targets, which may ultimately relieve their suffering from this
painful disease."



ZURAMPIC is also under regulatory review in the European Union and other
territories. On 18 December 2015, the Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion
recommending the marketing authorisation of ZURAMPIC 200mg tablets. ZURAMPIC, in
combination with an XOI, is recommended for the adjunctive treatment of
hyperuricaemia in gout patients (with or without tophi) who have not achieved
target sUA levels with an adequate dose of an XOI alone.

About ZURAMPIC® (lesinurad) 200mg tablets

ZURAMPIC® (lesinurad) 200mg tablets inhibits the urate transporter, URAT1, which
is responsible for the majority of the renal reabsorption of uric acid. By
inhibiting URAT1, ZURAMPIC increases uric acid excretion and thereby lowers
serum uric acid (sUA). ZURAMPIC also inhibits organic anion transporter (OAT) 4
a uric acid transporter involved in diuretic-induced hyperuricemia. In addition,
in people, ZURAMPIC does not inhibit OAT1 and OAT3, which are drug transporters
in the kidney associated with drug-drug interactions.

About the ZURAMPIC Development Programme

CLEAR1 and CLEAR2 (see prior release on this topic here (http://www.astrazeneca
-us.com/media/press-releases/Article/20141116-data-presented-from-phase-iii
-studies-of-lesinurad)) were pivotal Phase III studies that evaluated the
efficacy and safety of a once daily dose of ZURAMPIC in combination with
allopurinol compared to allopurinol alone. In CLEAR1 and CLEAR2, ZURAMPIC when
used in combination with allopurinol, met the primary endpoint in both studies
with approximately twice as many patients achieving the serum uric acid (sUA)
goal of <6.0mg/dL (360 µmol/L) by month 6, compared to those treated with
allopurinol alone.

CRYSTAL (see prior release on this topic here (http://www.astrazeneca
-us.com/media/press-releases/Article/20150612-eular-2015)) was a pivotal Phase
III study that evaluated the efficacy and safety of a once daily dose of
ZURAMPIC in combination with febuxostat 80mg compared to febuxostat 80mg alone
in gout patients with tophi (visible deposits of urate crystals in joints and
skin). Patients were administered febuxostat 80mg orally once daily for 3 weeks
before randomisation. In CRYSTAL, results showed ZURAMPIC 200mg in combination
with febuxostat demonstrated greater (nominal p<0.05) sUA lowering to the target
for tophaceous gout of <5.0mg/dL (300 µmol/L) compared to febuxostat alone at
all months except at the time of the primary endpoint, month 6 (56.6% vs. 46.8%,
non significant). In the subgroup of patients with baseline sUA ≥5.0mg/dL (300
µmol/L) (i.e. those above recommended sUA treatment target for tophaceous gout
on febuxostat alone), ZURAMPIC 200mg in combination with febuxostat resulted in
more subjects reaching target sUA of <5.0mg/dL (300 µmol/L) compared to
febuxostat alone at month 6.

In a pooled analysis of the three clinical trials, the safety profile was
similar for ZURAMPIC 200mg in combination with an XOI to that of an XOI alone,
with the exception of an increased incidence of predominantly reversible serum
creatinine (sCr) elevations.

About Hyperuricemia and Gout

Gout is a serious, chronic, progressive, and debilitating form of inflammatory
arthritis that affects more than 15.8 million people in major markets.* The
underlying cause of gout is hyperuricemia (elevated sUA), which leads to the
deposition of crystals primarily in the joints and in other tissues. This can
result in recurrent attacks of inflammatory arthritis and, if left uncontrolled,
could lead to chronic, progressive arthritis, and tophus (visible deposits of
urate crystals) formation.



The goal of sUA lowering treatment is to reduce sUA levels to the target level
of <6.0mg/dL (360 µmol/L) as recommended by both the American College of
Rheumatology (ACR) and the European League Against Rheumatism (EULAR). In those
with greater disease severity and urate burden, such as those with tophi,
guidelines recommend lowering sUA to <5.0mg/dL (300 µmol/L) to achieve better
disease control.

Among patients treated in clinical trials, less than 50% of patients on
allopurinol 300mg reached sUA target levels <6.0mg/dL (360 µmol/L). For patients
who cannot reach target on an XOI alone, the current ACR and EULAR guidelines
recommend adding an agent that increases uric acid excretion.

 *Major markets include the United States, France, Germany, Italy, Spain, the
United Kingdom and Japan

About Ardea Biosciences

Ardea Biosciences is a member of the AstraZeneca Group, located in San Diego,
California. Ardea is leading the development of AstraZeneca's gout portfolio,
including ZURAMPIC and RDEA3170. RDEA3170 is a potent selective uric acid
reabsorption inhibitor (SURI), also intended for use as a combination urate
lowering therapy with xanthine oxidase inhibitors (XOIs). RDEA3170 is our lead
investigational urate lowering therapy (ULT) in Asia and is currently entering a
Phase IIb trial worldwide.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation of prescription
medicines, primarily for the treatment of diseases in three main therapy areas -
respiratory, inflammation, autoimmune disease (RIA), cardiovascular and
metabolic disease (CVMD) and oncology - as well as in infection and
neuroscience. 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



23 December 2015

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