Ironwood Highlights ZURAMPIC® (lesinurad) Phase III Extension Study Data at the American College of Rheumatology 2016 Annual...
November 13 2016 - 8:00AM
Business Wire
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:
- 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.
- 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.
- 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.
- 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 GoutGout 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
tabletsZURAMPIC® (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
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 PharmaceuticalsIronwood
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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Ironwood PharmaceuticalsMedia RelationsTrista Morrison,
617-374-5095Director, Corporate
Communicationstmorrison@ironwoodpharma.comorInvestor
RelationsMeredith Kaya, 617-374-5082Director, Investor
Relationsmkaya@ironwoodpharma.com
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