Positive Phase 2 Data on RDEA594, Ardea Biosciences' Lead Product Candidate for the Treatment of Hyperuricemia and Gout, Presented at the Annual European Congress of Rheumatology
New Data from Five Clinical Studies Reinforce RDEA594's Robust Efficacy and Encouraging Safety Profile
ROME, June 18 /PRNewswire-FirstCall/ -- Ardea Biosciences, Inc.
(NASDAQ: RDEA) today announced that additional
positive data from its Phase 2 program for RDEA594, its lead
product candidate for the treatment of hyperuricemia and gout, are
being presented at the Annual European Congress of Rheumatology
hosted by the European League Against Rheumatism (EULAR) in Rome,
Italy. RDEA594, a first-in-class selective inhibitor of the URAT1
transporter, treats the underlying cause of gout by increasing the
excretion of uric acid in order to bring the body's levels of uric
acid into a normal range.
Highlights of the new data being presented at EULAR include:
-- Updated results from a Phase 2b monotherapy study of RDEA594 in 123
gout patients demonstrating a 60% response rate at the highest dose
tested.
-- Interim results from an ongoing Phase 1b study examining the
pharmacokinetics and pharmacodynamics of RDEA594 and allopurinol
separately and in combination that demonstrate a 100% response rate in
patients receiving two different doses of RDEA594 combined with
allopurinol.
-- Results from multiple studies indicating that the efficacy of RDEA594
is not diminished in patients with mild-to-moderate renal impairment.
-- Safety results from five clinical studies indicating that RDEA594 is
well tolerated alone or in combination with allopurinol or febuxostat
(Uloric®, Takeda Pharmaceutical Company Limited; Adenuric®, Ipsen and
Menarini), with no occurrence of drug-related serious adverse events
or dose-related side effects.
"We are pleased to see the very strong and consistent efficacy
data from these studies," said Barry D. Quart, PharmD, President
and Chief Executive Officer of Ardea Biosciences. "The interim
results from our ongoing Phase 1b study of RDEA594 in combination
with allopurinol and our completed proof-of-concept study with
febuxostat indicate we can achieve up to 80% mean reductions of
uric acid levels when combined with currently marketed agents for
the treatment of gout. These combinations would be among the most
potent uric acid lowering treatments available."
"RDEA594 has demonstrated a very consistent efficacy and safety
profile," stated Dr. Fernando Perez-Ruiz, Assistant Head of the
Rheumatology Division, Hospital de Cruces, Vizcaya, Spain. "New
data from the studies presented at EULAR not only position the drug
for Phase 3 studies, but further demonstrate RDEA594's potential to
be an important new therapy to treat the millions of gout patients
who are currently untreated or under-treated and continue to
experience painful and debilitating flares due to the inadequate
hypouricemic effect of approved therapies."
Updated Results from Phase 2b Monotherapy Study
Updated results from Ardea's Phase 2b study of RDEA594 given as
monotherapy are being presented in an oral presentation at EULAR.
One hundred twenty-three patients with gout and hyperuricemia were
randomized and dosed in this 28-day, double-blind,
placebo-controlled, dose-escalation study. The primary endpoint of
this study, which tested three doses of RDEA594 (200 mg, 400 mg and
600 mg) given once daily was the proportion of patients who
achieved a response, defined as a reduction of uric acid in the
blood to below 6 mg/dL after 4 weeks of treatment, compared to
placebo. The primary endpoint of the study was achieved, and serum
uric acid levels decreased and response rates increased in a
dose-related manner. The response rates on placebo, 200 mg RDEA594,
400 mg RDEA594 and 600 mg RDEA594 were 0%, 13%, 42% and 60%,
respectively. The response rates in both the 400 mg and 600 mg dose
groups were highly clinically and statistically significant. For
patients with baseline uric acid levels less than 10 mg/dL, who
represent the majority of gout patients in clinical practice,
response rates were 57% and 75% in the 400 mg and 600 mg dose
groups, respectively.
Updated Efficacy Results of Phase 2b Monotherapy Study of
RDEA594 in the Treatment of Hyperuricemia in Gout Patients
Treatment Groups
RDEA594 RDEA594 RDEA594
600 mg qd 400 mg qd 200 mg qd Placebo
Response Rate 60% 42% 13% 0%
(Primary Endpoint) (n = 32) (n = 33) (n = 31) (n = 27)
p Value versus
Placebo < 0.0001 0.0001 NS
Response Rate in Pts.
with Baseline Serum
Urate < 10 mg/dL 75% 57% 21% 0%
(n = 12) (n = 14) (n = 18) (n = 14)
p Value versus
Placebo 0.0001 0.0004 NS
NS = not statistically significant
The updated response rates from the results of this study are
higher than the preliminary, top-line results reported on March 31,
2010. This difference is due to a difference in the method used to
measure the levels of uric acid in the blood. The preliminary,
top-line results were generated using an indirect assay method
(UV), while the updated response data were generated using a
direct, more precise assay method (LC-MS/MS).
Initial Combination Therapy Results
In addition to an ongoing Phase 2b study examining the
combination of RDEA594 and allopurinol, Ardea is currently
conducting a Phase 1b, open-label clinical pharmacology study
examining the pharmacokinetics and pharmacodynamics (PK/PD) of this
combination. Interim results of this PK/PD study and final results
from a previously reported Phase 2a study of the combination of
RDEA594 and allopurinol are being presented at EULAR.
Allopurinol is the most widely prescribed drug currently
available to treat gout patients. However, recent controlled
studies have shown that less than 50% of patients reach target uric
acid reduction (sUA less than 6 mg/dL) on a standard allopurinol
dose of 300 mg per day. RDEA594 lowers excessive uric acid levels
(the underlying cause of gout) by increasing uric acid excretion,
while allopurinol decreases its production. Ardea believes that the
combination of RDEA594 with allopurinol may provide an important
treatment option for the significant portion of gout patients who
do not achieve adequate response to allopurinol treatment alone by
potentially enabling them to further reduce their uric acid levels
to within the normal range.
In the ongoing PK/PD study, patients receive a 300 mg dose of
allopurinol alone for one week, then allopurinol plus RDEA594 at a
dose of either 600 mg or 400 mg for one week, then RDEA594 at the
same dose alone for one week. Currently, 11 of approximately 20
patients planned have completed dosing in the study (mean baseline
sUA = 9.2 mg/dL).
Consistent with the combination results from a previously
reported Phase 2a study, interim results from this PK/PD study
indicate that combining RDEA594 with allopurinol produces greater
reductions in uric acid levels than observed with either agent
alone. As illustrated in the table below, 100% of patients in the
PK/PD study who have completed dosing on either 600 mg or 400 mg of
RDEA594 plus allopurinol reached target serum uric acid levels of
below 6 mg/dL. Furthermore, at the RDEA594 600 mg combination dose,
all patients who have completed dosing achieved a reduction to
below 5 mg/dL sUA. The combination has been well tolerated, with no
serious adverse events, no discontinuations, and no clinically
relevant changes in any laboratory parameter, except the desired
reduction in serum urate.
PK/PD Study Interim Results
sUA Response - % of Patients
Treatment Groups
Allopurinol 300 mg RDEA594 400 mg RDEA594 600 mg
Alone + Allopurinol 300 mg + Allopurinol 300 mg
(n = 11) (n = 6) (n = 5)
< 6 mg/dL 27% 100% 100%
< 5 mg/dL 9% 67% 100%
< 4 mg/dL 0% 0% 60%
Ardea is also studying the use of RDEA594 in combination with
febuxostat, which, like allopurinol works by decreasing uric acid
production. Data from a proof-of-concept study examining the
combination of RDEA594 and febuxostat are being presented at
EULAR.
In this randomized, placebo-controlled study in healthy
volunteers with serum uric acid levels generally above 6 mg/dL, the
combination of 400 mg of RDEA594 and 40 mg of febuxostat resulted
in an approximate 70% reduction of serum uric acid levels compared
to baseline, with intraday reductions of over 80%, reaching mean
serum uric acid levels of 1.2 mg/dL. These results demonstrate a
robust additive effect of combining RDEA594 and febuxostat when
compared to serum uric acid reductions of 49% and 45%,
respectively, when each drug was administered alone in this study.
There were no clinically relevant pharmacokinetic drug interactions
observed with either dose tested of RDEA594 and febuxostat. RDEA594
was well tolerated with adverse events that were generally mild and
transient, and no clinically significant laboratory abnormalities
were observed.
Results in Patients with Renal Impairment
In a previously reported Phase 2a study, the efficacy response
to RDEA594 in gout patients with mild-to-moderate renal impairment
did not differ from that observed in patients with normal renal
function. These earlier results were further confirmed by results
presented at EULAR from the Phase 2b monotherapy study, as well as
interim results from a study specifically evaluating the
pharmacokinetics and activity of RDEA594 in patients with moderate
renal impairment.
In the Phase 2b monotherapy study, 29 patients out of a total of
96 randomized to active drug had at least mild renal impairment.
Ten of these patients were classified as having moderate impairment
and had a mean creatinine clearance of 46 ml/min. Patients in the
Phase 2b study achieved comparable levels of uric acid reduction,
irrespective of renal function at baseline.
Ardea is also conducting a study designed specifically to
evaluate the pharmacokinetics and activity of RDEA594 in patients
with moderate renal impairment. Currently, four patients have
completed dosing in the study. Based upon an interim analysis of
completed patients, no meaningful change in the pharmacokinetics of
RDEA594 has been observed in gout patients with moderate renal
impairment. In addition, these patients showed an efficacy response
to RDEA594 comparable to that previously seen in gout patients with
normal renal function.
Overall Safety Results
RDEA594 was well tolerated alone or in combination with
allopurinol or febuxostat in the five studies presented at EULAR,
with no drug-related serious adverse events and no dose-related
side effects. In the Phase 2b monotherapy study, the incidence of
elevated serum creatinine levels was not significantly different
across the treatment groups, including placebo, after four weeks of
dosing. In addition, as previously reported and as presented at
EULAR, there was no difference in the rate of transient changes in
serum creatinine observed during the screening period, prior to
initiation of drug treatment, and during the treatment
period.
The EULAR presentations and posters will be available on the
Company's website (http://www.ardeabio.com/) under the following
titles following their presentation at the conference on June 18th
and 19th:
-- Efficacy and Safety of a Range of Doses of RDEA594, a Novel Uricosuric
Agent, as a Single Agent in Hyperuricemic Gout Patients: Multicenter,
Randomized, Double-Blind, Placebo-Controlled, Phase 2 Experience
-- RDEA684, a Novel, Potent and Efficacious Inhibitor of Human Urate
Transporter, URAT1, with a Favorable Pharmacokinetic Profile, and No
Mitochondrial Toxicity
-- Efficacy and Safety of RDEA594, a Novel Uricosuric Agent, as
Combination Therapy with Allopurinol in Gout Patients: Randomized,
Double-Blind, Placebo-Controlled, Phase 2 Experience
-- RDEA594, a Novel Uricosuric Agent, Shows Impressive Reductions in
Serum Urate Levels as Monotherapy and Substantial Additive Activity in
Combination with Febuxostat in Normal Healthy Volunteers
About Hyperuricemia and Gout
Gout is a painful and debilitating disease caused by abnormally
elevated levels of uric acid in the blood stream. This leads to the
deposition of painful, needle-like uric acid crystals in and around
the connective tissue of the joints and in the kidneys, resulting
in inflammation, the formation of disfiguring nodules (tophi),
intermittent attacks of severe pain (acute flares) and kidney
damage (nephropathy). In addition, evidence suggests that the
chronic elevation of uric acid associated with gout, known as
hyperuricemia, may also have systemic consequences, including an
increased risk for kidney dysfunction and cardiovascular
disease.
In 2008, approximately 5.2 million patients in the U.S., 6.4
million patients in the European Union and 2.9 million patients in
Japan were diagnosed with gout. Gout is the most common form of
inflammatory arthritis in men over 40 and represents a significant
medical need with limited treatment options. In the last 40 years,
only one new medication has received FDA approval for the treatment
of hyperuricemia associated with gout.
About RDEA594
Our most advanced product candidate for the treatment of
hyperuricemia and gout, RDEA594, is a selective inhibitor of URAT1,
a transporter in the kidney that regulates uric acid excretion from
the body. Approximately 90% of gout patients are considered to be
under-excretors of uric acid, and recent studies have shown that
defects in renal transporters have been genetically linked to gout.
Consequently, increasing renal excretion of uric acid by moderating
URAT1 transporter activity may provide the most physiologically
appropriate treatment for gout. In addition, because increasing the
excretion of serum uric acid is additive to the effects of drugs
such as allopurinol that decrease the production of uric acid,
RDEA594 in combination with such drugs has the potential to treat
the significant portion of the gout population that is not
adequately treated with existing therapies.
RDEA594 is in Phase 2 development as a single agent and in
combination with the approved xanthine oxidase inhibitor,
allopurinol. Over 500 people have received RDEA594, either by
direct administration in the form currently in development or
through administration of RDEA806, a prodrug of RDEA594.
About Ardea Biosciences, Inc.
Ardea Biosciences, Inc., of San Diego, California, is a
biotechnology company focused on the development of small-molecule
therapeutics for the treatment of gout, cancer and human
immunodeficiency virus (HIV). RDEA594, our lead product candidate
for the treatment of hyperuricemia and gout, is a selective URAT1
transporter inhibitor in Phase 2 clinical development. Our
next-generation URAT1 inhibitor program is currently in preclinical
development. RDEA119, a potent and specific inhibitor of
mitogen-activated ERK kinase (MEK) and our lead product candidate
for the treatment of cancer, is being developed under a global
license agreement with Bayer HealthCare AG. RDEA119 is currently
being evaluated in advanced cancer patients with different tumor
types as a single agent in a Phase 1 study as well as in
combination with sorafenib (Nexavar®; Bayer HealthCare, Onyx
Pharmaceuticals) in a Phase 1/2 study. Our two product candidates
for the treatment of HIV, RDEA806 and RDEA427, are non-nucleoside
reverse transcriptase inhibitors (NNRTIs), which have successfully
completed a Phase 2a study in HIV patients and a human micro-dose
pharmacokinetic study in healthy volunteers, respectively.
Statements contained in this press release regarding matters
that are not historical facts are "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Such
statements include, but are not limited to, statements regarding
our plans and goals, the expected properties and benefits of
RDEA594, RDEA119, RDEA806, RDEA427 and our other compounds and the
timing and results of our preclinical, clinical and other studies.
Risks that contribute to the uncertain nature of the
forward-looking statements include risks related to the outcome of
preclinical and clinical studies, risks related to regulatory
approvals, delays in commencement of preclinical and clinical
studies, costs associated with our drug discovery and development
programs, and risks related to the outcome of our business
development activities. These and other risks and uncertainties are
described more fully in our most recently filed SEC documents,
including our Annual Report on Form 10-K and our Quarterly Reports
on Form 10-Q, under the headings "Risk Factors." All
forward-looking statements contained in this press release speak
only as of the date on which they were made. We undertake no
obligation to update such statements to reflect events that occur
or circumstances that exist after the date on which they were
made.
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CONTACT: Ardea, John Beck of Ardea Biosciences, Inc.,
+1-858-652-6523,
jbeck@ardeabio.com; or Media, Heidi
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for Ardea Biosciences,
Inc.
Web Site: http://www.ardeabiosciences.com/
Posted: June 2010
