-- Initial data from investigator-initiated
TRIPLE study shows infusion reactions occurred in less than 1
percent of infusions --
Horizon Pharma plc (NASDAQ:HZNP), a biopharmaceutical company
focused on improving patients' lives by identifying, developing,
acquiring and commercializing differentiated and accessible
medicines that address unmet medical needs, today announced new
data evaluating KRYSTEXXA® (pegloticase injection) will be shared
in four poster presentations this week at the 2017 ACR/ARHP Annual
Meeting, Nov. 3-8, in San Diego. These data include initial
results from an investigator-initiated dosing study, as well as
three post-hoc analyses of KRYSTEXXA clinical trials, and are part
of Horizon Pharma’s ongoing efforts to advance the science and
ultimately improve outcomes for people living with chronic gout
refractory to conventional therapies, also known as uncontrolled
gout.
“We’ve heard many firsthand accounts of the debilitating pain
experienced by people living with uncontrolled gout and are driven
to further our research and understanding of KRYSTEXXA for those
who continue to suffer from agonizing symptoms and associated
health problems like high blood pressure or chronic kidney
disease,” said Jeffrey W. Sherman, M.D., FACP, executive vice
president, research and development and chief medical officer,
Horizon Pharma plc. “By partnering with the leaders in the
scientific community, Horizon Pharma has made significant progress
improving the understanding of KRYSTEXXA's safety profile.
The TRIPLE study incorporated many of these learnings and the
results show that proper utilization of the KRYSTEXXA stopping
rules may reduce the risk for infusion reactions.”
The initial results from the investigator-initiated TRIPLE
(Tolerization Reduces
Intolerance to Pegloticase and
Prolongs the Urate Lowering
Effect) study presented today at ACR/ARHP offer
further understanding into factors that influence response and show
a notable reduction in the frequency of infusion reactions
(IRs). Additionally, data from the three post-hoc analyses of
KRYSTEXXA show the connection of lower serum uric acid (sUA) levels
to a reduction in blood pressure, a reduction in tophi and an
ability for patients to reach complete response (CR).
"TRIPLE is the first study to show prospectively that when
treatment ‘stopping rules’ are used, which is occurring more
frequently in real-world practice, the rate of infusion reactions
can be meaningfully reduced," said Peter E. Lipsky, M.D., one of
the authors of the poster presentation and director of clinical
operations for AMPEL BioSolutions. “We saw a remarkable
decrease in the frequency of infusion reactions during this
study. Further research through TRIPLE and continued
evaluation will help to clarify factors that influence response
such as tolerization dose, schedule, demographic factors and the
utilization of concomitant immunomodulation.”
Data Summaries Presented at ACR/ARHP 2017
Initial Results of a Clinical Study to Determine Whether
a Tolerizing Regimen of Pegloticase Can Increase the Frequency of
Subjects Having Sustained Lowering of Serum Urate
(abstract
1141)Initial results presented
from an ongoing investigator-initiated TRIPLE study show the
tolerization regimen was well-tolerated in people living with
uncontrolled gout. The emerging data indicates an overall
response rate of 44 percent when adding an additional tolerizing
dose of KRYSTEXXA between the first and second biweekly
administrations. TRIPLE is the first prospective study
evaluating the recommended ‘stopping rules’ developed to avoid the
development of IRs. Results demonstrate that a reduction in
the rate of IRs can occur, with IRs from this study associated with
less than one percent of the infusions.
- The poster presentation at ACR/ARHP included data from 50
uncontrolled gout patients who received a total of 315 infusions in
this multicenter, open-label dosing study.
- Out of 315 doses of KRYSTEXXA administered, only one mild IR
occurred (0.3 percent) in a single patient, which did not meet the
criteria for anaphylaxis.
- The most common adverse event (AE) reported was a gout
flare. A total of 26 patients (52 percent) experienced gout
flares.
- The AEs were mostly mild to moderate (92 percent). Eight
serious adverse events were reported – three were considered to be
unrelated to KRYSTEXXA and five were characterized as a severe gout
flare.
- Seven patients (14 percent) discontinued treatment before
completing the study.
Treatment with Pegloticase Significantly Decreases Mean
Arterial Blood Pressure in Patients with Chronic Gout
(abstract
2067) Data from this
post-hoc analysis provides valuable insights on connections between
sUA levels and blood pressure for people living with uncontrolled
gout treated with KRYSTEXXA. Such patients often have other
health conditions that are closely associated with high blood
pressure, such as chronic kidney disease.1
The analysis of 173 patients with uncontrolled gout included
data from two pivotal, six-month clinical trials in which patients
were randomized to treatment with KRYSTEXXA every two or four weeks
or placebo. Results show that 62.1 percent of patients who
received KRYSTEXXA every two weeks, and were characterized as sUA
responders by the prespecified primary endpoint, experienced
meaningful reductions in mean arterial blood pressure throughout
the trials. These reductions were independent of changes in
renal function. A similar analysis was recently presented at
the American Society of Nephrology (ASN) Kidney Week 2017.
While the studies in these analyses were not designed to
evaluate change in mean arterial blood pressure as a clinical
endpoint, these findings support further investigation of KRYSTEXXA
in blood pressure reduction.
Evidence-Based Development of Criteria for Complete
Response in Patients with Chronic Refractory Gout
(abstract 2070)
In a post-hoc analysis of two pivotal,
identical, six-month, randomized clinical trials and an open-label
study of uncontrolled gout patients, the majority of uncontrolled
gout patients treated with KRYSTEXXA who had persistently lower sUA
also reached criteria for remission and did so within one year from
the initiation of therapy. The trials were controlled up to
six months, with a portion of patients continuing in an open-label
study and forming the basis of this post-hoc analysis.
Forty-two percent of uncontrolled gout patients met the
prespecified primary endpoint for complete response, and 85.3
percent of these patients met the published criteria for
remission. The mean time from the beginning of the clinical
trials to reach remission was 11.5 months. All patients who
achieved a remission maintained response until the end of follow-up
(mean duration of remission was 507.4 days).
Rapid Tophus Resolution in Chronic Refractory Gout
Patients Treated with Pegloticase
(abstract
2054)Data from a post-hoc
analysis of two pivotal, six-month, randomized clinical trials and
open-label study indicates rapid resolution of tophi was observed
in patients with uncontrolled gout characterized as sUA responders
by the prespecified primary endpoint. The trials were
controlled up to six months, with a portion of patients continuing
in an open-label study and forming the basis of this post-hoc
analysis. Serial standardized digital images of 260 tophi
were analyzed for 87 patients with uncontrolled gout, 23 of whom
were sUA responders, and showed the velocity of tophus reduction
was 60.2 mm² per month in sUA responders over the course of the
trials with a mean time for complete resolution of tophi at 132
days.
Gout is a type of chronic inflammatory arthritis in which uric
acid builds up in the blood and can lead to severe pain and joint
destruction. Patients with uncontrolled gout continue to have
abnormally high levels of uric acid and continued symptoms despite
the use of conventional therapies. KRYSTEXXA is the only
medicine approved by the U.S. Food and Drug Administration (FDA)
for the treatment of uncontrolled gout in adult patients. For
more information, please visit www.KRYSTEXXAHCP.com
About KRYSTEXXA® INDICATIONS AND
USAGEKRYSTEXXA® (pegloticase injection) is a PEGylated
uric acid specific enzyme indicated for the treatment of chronic
gout in adult patients refractory to conventional therapy.
Gout refractory to conventional therapy occurs in patients who
have failed to normalize serum uric acid and whose signs and
symptoms are inadequately controlled with xanthine oxidase
inhibitors at the maximum medically appropriate dose or for whom
these drugs are contraindicated.
Important Limitations of Use: KRYSTEXXA is not
recommended for the treatment of asymptomatic
hyperuricemia.
IMPORTANT SAFETY INFORMATIONWARNING:
ANAPHYLAXIS AND INFUSION REACTIONS
Anaphylaxis and infusion reactions have been reported to occur
during and after administration of KRYSTEXXA. Anaphylaxis may
occur with any infusion, including a first infusion, and generally
manifests within 2 hours of the infusion. However,
delayed-type hypersensitivity reactions have also been reported.
KRYSTEXXA should be administered in healthcare settings and
by healthcare providers prepared to manage anaphylaxis and infusion
reactions. Patients should be premedicated with
antihistamines and corticosteroids. Patients should be
closely monitored for an appropriate period of time for anaphylaxis
after administration of KRYSTEXXA. Serum uric acid levels
should be monitored prior to infusions, and healthcare providers
should consider discontinuing treatment if levels increase to above
6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are
observed.
The risk of anaphylaxis and infusion reactions is higher in
patients who have lost therapeutic response.
Concomitant use of KRYSTEXXA and oral urate-lowering agents may
blunt the rise of sUA levels. Patients should discontinue
oral urate-lowering agents and not institute therapy with oral
urate-lowering agents while taking KRYSTEXXA.
In the event of anaphylaxis or infusion reaction, the infusion
should be slowed, or stopped and restarted at a slower rate.
Patients should be informed of the symptoms and signs of
anaphylaxis and instructed to seek immediate medical care should
anaphylaxis occur after discharge from the healthcare setting.
CONTRAINDICATIONS: G6PD DEFICIENCY ASSOCIATED
HEMOLYSIS AND METHEMOGLOBINEMIAPatients should be screened
patients for G6PD deficiency prior to starting KRYSTEXXA.
Hemolysis and methemoglobinemia have been reported with
KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA should
not be administered to these patients.
GOUT FLARESAn increase in gout flares is
frequently observed upon initiation of anti-hyperuricemic therapy,
including treatment with KRYSTEXXA. If a gout flare occurs
during treatment, KRYSTEXXA need not be discontinued. Gout
flare prophylaxis with a non-steroidal anti-inflammatory drug
(NSAID) or colchicine is recommended starting at least 1 week
before initiation of KRYSTEXXA therapy and lasting at least 6
months, unless medically contraindicated or not tolerated.
CONGESTIVE HEART FAILUREKRYSTEXXA has not been
studied in patients with congestive heart failure, but some
patients in the clinical trials experienced exacerbation.
Caution should be exercised when using KRYSTEXXA in patients who
have congestive heart failure, and patients should be monitored
closely following infusion.
ADVERSE REACTIONSThe most commonly reported
adverse reactions in clinical trials with KRYSTEXXA were gout
flares, infusion reactions, nausea, contusion or ecchymosis,
nasopharyngitis, constipation, chest pain, anaphylaxis and
vomiting.
Horizon Pharma plc Horizon Pharma plc is a
biopharmaceutical company focused on improving patients' lives by
identifying, developing, acquiring and commercializing
differentiated and accessible medicines that address unmet medical
needs. The Company markets 11 medicines through its orphan,
rheumatology and primary care business units. For more
information, please visit www.horizonpharma.com.
Follow @HZNPplc on Twitter, like us on Facebook or
view careers on our LinkedIn page.
Forward-Looking Statements This press
release contains forward-looking statements, including, but not
limited to, statements related to the benefits of KRYSTEXXA to
patients with uncontrolled gout, the potential for dosing
strategies to increase effectiveness of KRYSTEXXA, and other
statements that are not historical facts. These
forward-looking statements are based on Horizon Pharma's current
expectations and inherently involve significant risks and
uncertainties. Actual results and the timing of events could
differ materially from those anticipated in such forward looking
statements as a result of these risks and uncertainties, which
include, without limitation, the fact that results in ongoing
clinical trials may not support better patient outcomes from the
use of KRYSTEXXA, as well as other risks related to Horizon
Pharma's business detailed from time-to-time under the caption
"Risk Factors" and elsewhere in Horizon Pharma's SEC filings and
reports, including in its Annual Report on Form 10-K for the year
ended December 31, 2016 and subsequent quarterly reports on Form
10-Q. Horizon Pharma undertakes no duty or obligation to
update any forward-looking statements contained in this press
release as a result of new information, future events or changes in
its expectations.
References1 National Kidney Foundation. A
to Z Health Guide: Gout, Hyperuricemia and Chronic Kidney Disease.
Web. October 11, 2017. https://www.kidney.org/atoz/content/gout
Contacts:Tina VenturaSenior Vice President,
Investor RelationsInvestor-relations@horizonpharma.com
Ruth VenningExecutive Director, Investor
RelationsInvestor-relations@horizonpharma.com
U.S. Media Contact:Amanda PhranerSenior
Manager, Public Relations and Social
Mediamedia@horizonpharma.com
Ireland Media Contact:Ray GordonGordon
MRMray@gordonmrm.ie
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