If approved, DUZALLO would be first dual-mechanism treatment for
patients with uncontrolled gout
CAMBRIDGE, Mass.--(BUSINESS WIRE)--
Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) today announced the U.S. Food
and Drug Administration (FDA) accepted for review a New Drug Application
(NDA) for DUZALLO™ (fixed-dose combination of lesinurad and allopurinol)
for the treatment of hyperuricemia in patients with uncontrolled gout.
The FDA Prescription Drug User Fee Act (PDUFA) target action date is
expected to occur in the second half of 2017 and, if approved, DUZALLO
is expected to be commercially available in late 2017.
It is estimated that approximately half of the four million gout
patients in the U.S. treated with a xanthine oxidase inhibitor (XOI),
either allopurinol or febuxostat, are uncontrolled and are not achieving
target serum uric acid (sUA) levels < 6 mg/dL as recommended by the
American College of Rheumatology. Lesinurad is currently approved by the
FDA under the brand name ZURAMPIC® to be taken in combination with an
XOI for the treatment of hyperuricemia - high levels of uric acid in the
blood - associated with gout in patients who have not achieved target
sUA levels with an XOI alone. ZURAMPIC is not recommended for the
treatment of asymptomatic hyperuricemia and should not be used as
monotherapy.
Lesinurad is a once-daily oral tablet that lowers sUA by reducing
reabsorption of uric acid, thereby increasing renal excretion of uric
acid. The mechanism of lesinurad is distinct from and complementary to
that of an XOI, which reduces production of uric acid. Together, the
dual-mechanism combination of lesinurad plus an XOI can address both
inefficient excretion and overproduction of uric acid. Currently,
patients with uncontrolled gout are often treated with higher doses of
XOIs that may require multiple pills daily in an attempt to reach their
sUA target. If approved, DUZALLO would be the first treatment to offer
this dual-mechanism of action in a single pill to be taken once per day.
The NDA for DUZALLO is based on the extensive clinical program
supporting the ZURAMPIC NDA and a pharmacokinetic study that evaluated
the bioequivalence of the fixed-dose combination of lesinurad and
allopurinol compared to co-administration of separate lesinurad and
allopurinol tablets. The efficacy and safety of the two drugs
co-administered separately was demonstrated in two pivotal Phase III
clinical trials, CLEAR 1 and CLEAR 2, which supported the ZURAMPIC NDA.
In these clinical trials in adult patients with gout who failed to
achieve target sUA levels on allopurinol alone, the addition of ZURAMPIC
nearly doubled the number of patients who achieved sUA target of < 6
mg/dL at month 6, reduced the mean sUA to < 6 mg/dL by month 1 and
maintained that level through month 12. Acute renal failure has occurred
with ZURAMPIC and was more common when ZURAMPIC was given alone. The
most common adverse reactions with ZURAMPIC in the clinical trials were
headache, influenza, blood creatinine increased, and gastroesophageal
reflux disease. The DUZALLO NDA was submitted by Ardea BioSciences on
behalf of Ironwood.
About Hyperuricemia and Gout
Gout is a highly symptomatic
and painful form of inflammatory arthritis affecting more than nine
million people in the U.S. It is caused by an underlying metabolic
disorder, hyperuricemia - high levels of uric acid in the blood - and
can lead to painful flares, characterized by excruciating pain,
inflammation, swelling and tenderness in one or more joints. Gout has a
hereditary component and is not only a lifestyle disease. While diet and
lifestyle changes are important in managing gout and its comorbidities,
they are often not enough to get patient serum uric acid (sUA) levels to
target.
More than four million patients are treated with a xanthine oxidase
inhibitor (XOI), either allopurinol or febuxostat, for gout in the U.S.
Of these, an estimated two million patients are uncontrolled and are not
achieving target serum uric acid (sUA) levels < 6 mg/dL as recommended by
the American College of Rheumatology (ACR), despite treatment with an
XOI alone. These patients continue to suffer from flares, and may face
serious long-term consequences that can result from having uncontrolled
sUA levels. ACR guidelines recommend adding a uricosuric agent, like
ZURAMPIC, to an XOI in patients who are not achieving target sUA levels.
About lesinurad
Lesinurad is a URAT1 inhibitor approved by
the FDA for use 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.
Lesinurad is not recommended for the treatment of asymptomatic
hyperuricemia and should not be used as a monotherapy. XOIs reduce the
production of uric acid; lesinurad increases renal excretion of uric
acid by selectively inhibiting the action of URAT1, the UA transporter
responsible for the majority of renal UA reabsorption. The
dual-mechanism combination of lesinurad plus an XOI (allopurinol or
febuxostat) can address both inefficient excretion and overproduction of
UA, thereby lowering sUA levels. The safety profile and efficacy of
lesinurad were established in three Phase III clinical trials that
evaluated a once-daily dose of lesinurad in combination with the XOI
allopurinol or febuxostat compared to XOI alone. Lesinurad is marketed
by Ironwood in the U.S. as ZURAMPIC®; see the important
safety information below for more information.
About allopurinol
Allopurinol is a xanthine oxidase
inhibitor. Allopurinol's action differs from that of uricosuric agents
such as lesinurad. Allopurinol reduces both the serum and urinary uric
acid levels by inhibiting the formation of uric acid. The most frequent
adverse reaction to allopurinol is skin rash. Skin reactions can be
severe and sometimes fatal. The incidence of skin rash may be increased
in the presence of renal insufficiency.
ZURAMPIC Important Safety Information
WARNING: RISK OF ACUTE RENAL FAILURE MORE COMMON WHEN USED WITHOUT A
XANTHINE OXIDASE INHIBITOR (XOI)
-
Acute renal failure has occurred with ZURAMPIC and was more common
when ZURAMPIC was given alone
-
ZURAMPIC should be used in combination with an XOI
Contraindications:
-
Severe renal impairment (eCLcr less than 30 mL/min), end-stage renal
disease, kidney transplant recipients, or patients on dialysis
-
Tumor lysis syndrome or Lesch-Nyhan syndrome
Warnings and Precautions:
-
Renal events: Adverse reactions related to renal function have
occurred after initiating ZURAMPIC. A higher incidence was observed at
the 400-mg dose, with the highest incidence occurring with monotherapy
use. Monitor renal function at initiation and during therapy with
ZURAMPIC, particularly in patients with eCLcr below 60 mL/min or with
serum creatinine elevations 1.5 to 2 times the pre-treatment value,
and evaluate for signs and symptoms of acute uric acid nephropathy.
Interrupt treatment with ZURAMPIC if serum creatinine is elevated to
greater than 2 times the pre-treatment value or if there are symptoms
that may indicate acute uric acid nephropathy. ZURAMPIC should not be
restarted without another explanation for the serum creatinine
abnormalities. ZURAMPIC should not be initiated in patients with an
eCLcr less than 45 mL/min.
-
Cardiovascular events: In clinical trials, major adverse
cardiovascular events (defined as cardiovascular deaths, non-fatal
myocardial infarctions, or non-fatal strokes) were observed with
ZURAMPIC. A causal relationship has not been established.
Adverse Reactions:
-
Most common adverse reactions with ZURAMPIC (in combination with an
XOI and more frequently than on an XOI alone) were headache,
influenza, blood creatinine increased, and gastroesophageal reflux
disease.
Indication and Limitations of Use for ZURAMPIC:
ZURAMPIC is
a URAT1 inhibitor indicated in combination with an XOI for the treatment
of hyperuricemia associated with gout in patients who have not achieved
target serum uric acid levels with an XOI alone.
-
ZURAMPIC is not recommended for the treatment of asymptomatic
hyperuricemia
-
ZURAMPIC should not be used as monotherapy
Please see full Prescribing Information, including Boxed WARNING, http://www.azpicentral.com/zurampic/zurampic.pdf
About Ironwood Pharmaceuticals
Ironwood
Pharmaceuticals (NASDAQ: IRWD) is a commercial biotechnology company
focused on creating medicines that make a difference for patients,
building value for our fellow shareholders, and empowering our
passionate team. We are advancing a pipeline of innovative medicines in
areas of significant unmet need, including irritable bowel syndrome with
constipation (IBS-C)/chronic idiopathic constipation (CIC), uncontrolled
gout, refractory gastroesophageal reflux disease, and vascular and
fibrotic diseases. We discovered, developed and are commercializing
linaclotide, the U.S. branded prescription market leader in the
IBS-C/CIC category, and we are applying our proven R&D and commercial
capabilities to advance multiple internally-developed and
externally-accessed product opportunities. Ironwood was founded in 1998
and is headquartered in Cambridge, Mass. For more information, please
visit www.ironwoodpharma.com or www.twitter.com/ironwoodpharma;
information that may be important to investors will be routinely posted
in both these locations.
This press release contains forward-looking statements. Investors are
cautioned not to place undue reliance on these forward-looking
statements, including statements about FDA approval of, and the PDUFA
target action date for, DUZALLO, the commercial availability of DUZALLO
and the timing thereof, the potential benefits of DUZALLO and prevalence
and unmet need. Each forward‐looking statement is subject to risks and
uncertainties that could cause actual results to differ materially from
those expressed or implied in such statement. Applicable risks and
uncertainties include those related to the effectiveness of
commercialization efforts by Ironwood; efficacy, safety and tolerability
of lesinurad; decisions by regulatory authorities; challenges from and
rights of competitors or potential competitors; and those risks listed
under the heading "Risk Factors" and elsewhere in Ironwood's Quarterly
Report on Form 10-Q for the quarter ended September 30, 2016, and in our
subsequent SEC filings. These forward-looking statements (except as
otherwise noted) speak only as of the date of this press release, and
Ironwood undertakes no obligation to update these forward-looking
statements.
ZURAMPIC® and DUZALLOTM are trademarks owned by
AstraZeneca AB. Any other trademarks referred to in this press release
are the property of their respective owners. All rights reserved.
View source version on businesswire.com: http://www.businesswire.com/news/home/20170104005790/en/
Ironwood Pharmaceuticals, Inc.
Media Relations
Trista
Morrison, 617-374-5095
Director, Corporate Communications
tmorrison@ironwoodpharma.com
or
Investor
Relations
Meredith Kaya, 617-374-5082
Director, Investor
Relations
mkaya@ironwoodpharma.com
Source: Ironwood Pharmaceuticals, Inc.
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