[November 13, 2016] |
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Ironwood Highlights ZURAMPIC® (lesinurad) Phase III Extension Study Data at the American College of Rheumatology 2016 Annual Meeting
Ironwood
Pharmaceuticals, Inc. (NASDAQ: IRWD) today presented efficacy and
safety data from two Phase III extension studies of ZURAMPIC
(lesinurad), as well as pooled analyses from the two extension studies
and from the three pivotal Phase III ZURAMPIC clinical trials, in four
poster presentations at the American College of Rheumatology (ACR)
Annual Meeting in Washington, D.C.
ZURAMPIC is FDA-approved as a once-daily oral tablet to be taken 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 is not
recommended for the treatment of asymptomatic hyperuricemia and should
not be used as monotherapy.
The FDA approval of lesinurad was based upon three pivotal Phase III
trials: the CLEAR 1 and CLEAR 2 trials, in which patients were
randomized to receive either 200 mg lesinurad plus the XOI allopurinol,
400 mg lesinurad plus allopurinol, or placebo plus allopurinol for 12
months, and the CRYSTAL trial, in which patients were randomized to
receive 200 mg lesinurad plus the XOI febuxostat, 400 mg lesinurad plus
febuxostat, or placebo plus febuxostat for 12 months. The two lesinurad
extension studies, which were open-label, further evaluated the safety
and efficacy of lesinurad plus an XOI over a 12-month extension period.
The CLEAR extension study enrolled patients from the CLEAR 1 and CLEAR 2
trials, with patients who received lesinurad plus allopurinol in those
trials continuing their treatment, while patients who previously
received placebo were randomized to a lesinurad plus allopurinol
treatment arm. The CRYSTAL extension study enrolled patients from the
CRYSTAL trial, with patients who received lesinurad plus febuxostat in
that trial continuing their treatment, while patients who previously
received placebo were randomized to a lesinurad plus febuxostat
treatment arm.
Data are to be presented on Sunday, November 13, from 9:00 a.m. to
11:00 a.m. Eastern Time as follows:
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Examination of Serum Uric Acid (sUA) Lowering and Safety With
Extended Lesinurad + Allopurinol Treatment in Subjects With Gout (abstract
#208), to be presented by Kenneth G. Saag, M.D., M.Sc., University of
Alabama at Birmingham, during the Metabolic and Crystal Arthropathies
Poster Session I: Clinical Practice. This analysis found that patients
treated with lesinurad plus allopurinol in the CLEAR 1 and CLEAR 2
trials who continued treatment in the CLEAR extension study maintained
target sUA levels over the full two years. Additionally, an increased
proportion of patients who received placebo in CLEAR 1 and CLEAR 2
reached target sUA levels after crossing into the CLEAR extension
study and receiving treatment with lesinurad plus allopurinol. The
data from this extension study identified no new safety signals in
patients continuing lesinurad plus allopurinol treatment in the CLEAR
extension study relative to the safety profile observed for those
receiving lesinurad plus allopurinol in CLEAR 1 and CLEAR 2.
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Clinical Response of Tophus and Flares to Extended Use of
Lesinurad in Combination With a Xanthine Oxidase Inhibitor in Patients
With Gout (abstract #209), to be presented by Thomas Bardin,
M.D., Lariboisière Hospital, Paris, France, during the Metabolic and
Crystal Arthropathies Poster Session I: Clinical Practice. This
analysis of pooled data from patients receiving lesinurad plus XOI in
the CLEAR 1, CLEAR 2 or CRYSTAL trials who continued treatment in the
CLEAR and CRYSTAL extension studies examined the impact of treatment
of lesinurad plus XOI on tophi and flares. The pooled analysis found
that patients treated with lesinurad plus an XOI for up to two years
exhibited continued increases in the rate of complete resolution of
tophi and reduction in tophus area, as well as decreased rates of gout
flares.
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Renal Safety of Lesinurad: A Pooled Analysis of Phase III and
Extension Studies (abstract #206), to be presented by
Robert Terkeltaub, M.D., University of California, San Diego, during
the Metabolic and Crystal Arthropathies Poster Session I: Clinical
Practice. In this study, renal-related and kidney stone safety data
were pooled from patients enrolled in the CLEAR 1, CLEAR 2 and CRYSTAL
trials taking either lesinurad 200 mg plus XOI or lesinurad 400 mg
plus XOI as well as patients enrolled in the CLEAR and CRYSTAL
extension studies. These pooled safety data were compared against
patients taking XOI alone in the three pivotal Phase III trials, to
evaluate the impact on renal safety of extended lesinurad plus XOI
treatment. The study concluded that, except for a higher rate of serum
creatinine elevations, the majority of which resolved during the study
period, lesinurad at the approved dose of 200 mg once-daily combined
with an XOI demonstrated a comparable rate of renal adverse events to
XOI alone. There was no clinically relevant increase in these adverse
events with the extension of treatment beyond one year.
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Integrated Safety of Lesinurad, A Novel Uric Acid Reabsorption
Inhibitor for the Treatment of Gout (abstract #207), to be
presented by Michael A. Becker, M.D., University of Chicago, during
the Metabolic and Crystal Arthropathies Poster Session I: Clinical
Practice. This study integrated safety data for lesinurad based on
patients who completed the CLEAR 1, CLEAR 2 and CRYSTAL trials taking
either lesinurad 200 mg plus XOI or lesinurad 400 mg plus XOI, as well
as the CLEAR and CRYSTAL extension studies. The integrated study
concluded that lesinurad at the FDA-approved dose of 200 mg once-daily
combined with an XOI demonstrated a consistent, acceptable safety
profile, with rates of treatment-emergent adverse events comparable to
XOI alone and lower than with lesinurad 400 mg once-daily plus XOI.
There were no new safety concerns identified in the extension studies.
About Hyperuricemia and Gout Gout is a highly symptomatic
and painful form of inflammatory arthritis affecting an estimated eight
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 is
commonly hereditary and 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.
Approximately 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 ZURAMPIC® (lesinurad) 200 mg tablets ZURAMPIC®
(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. ZURAMPIC is not
recommended for the treatment of asymptomatic hyperuricemia and should
not be used as a monotherapy. XOIs reduce the production of uric acid;
ZURAMPIC 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
ZURAMPIC plus an XOI (allopurinol or febuxostat) can address both
inefficient excretion and overproduction of UA, thereby lowering sUA
levels. The safety and efficacy of ZURAMPIC were established in three
Phase III clinical trials that evaluated a once-daily dose of ZURAMPIC
in combination with the XOI allopurinol or febuxostat compared to XOI
alone. Visit www.zurampic.com
for more information about ZURAMPIC.
Important Safety Information
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WARNING: RISK OF ACUTE RENAL FAILURE MORE COMMON WHEN USED
WITHOUT A XANTHINE OXIDASE INHIBITOR (XOI)
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-- Acute renal failure has occurred with ZURAMPIC and was more
common when ZURAMPIC was given alone
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-- ZURAMPIC should be used in combination with an XOI
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Contraindications:
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Severe renal impairment (eCLcr less than 30 mL/min), end-stage renal
disease, kidney transplant recipients, or patients on dialysis
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Tumor lysis syndrome or Lesch-Nyhan syndrome
Warnings and Precautions:
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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.
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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:
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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.
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ZURAMPIC is not recommended for the treatment of asymptomatic
hyperuricemia
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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.
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