-- Seventy-Nine Percent of Patients Achieved a
Complete Response --
-- New Data Continues to Support
Immunomodulation Strategy to Improve Patient Outcomes --
Horizon Therapeutics plc (Nasdaq: HZNP) announced today topline
results from its MIRROR open-label study in which methotrexate with
KRYSTEXXA® (pegloticase injection) provided an increased durability
of response for people living with chronic gout refractory to
conventional therapies – also known as uncontrolled gout.
Data from the Methotrexate to Increase
Response Rates in Patients With Uncontrolled
GOut Receiving KRYSTEXXA (MIRROR OL) shows that 79
percent, or 11 of 14 patients, achieved a complete response,
defined as the proportion of serum uric acid (sUA) responders (sUA
< 6 mg/dL) at Month 6. Detailed results from the study will be
presented at a future medical meeting. The co-prescription of
KRYSTEXXA and methotrexate is investigational and its safety and
efficacy have not been established.
KRYSTEXXA has demonstrated rapid reduction in sUA levels for
people with uncontrolled gout; however, treatment with biologic
medicines can, in some, trigger the body’s immune system to develop
anti-drug antibodies. These anti-drug antibodies can reduce the
effectiveness of the biologic therapy. Immunomodulators such as
methotrexate, which is commonly used by rheumatologists, can help
reduce this reaction.
The MIRROR open-label pilot study follows other studies that
showed an improved response rate when KRYSTEXXA is co-administered
with methotrexate. This includes an independent case series
presented at the Annual European Congress of Rheumatology meeting
in June 2019 in which the administration of KRYSTEXXA with
methotrexate resulted in a 100 percent response (10 of 10 patients)
as defined by greater than 80 percent of sUA levels being
maintained at goal (<6.0 mg/dL) during the treatment period.1
Further, a separate case series presented at the American College
of Rheumatology meeting in November 2019 resulted in an 80 percent
response (8 of 10 patients) as defined by receiving ≥12 infusions
without loss of sUA response.2
“There is a growing body of data supporting the potential of
KRYSTEXXA plus methotrexate rather than KRYSTEXXA therapy alone,”
said Paul Peloso, M.D., M.Sc., vice president and therapeutic area
head, rheumatology, Horizon. “We continuously evaluate our
therapies to ensure every patient can achieve the best possible
outcomes. With a 79 percent response rate in combination with
methotrexate, which is significantly higher than the 42 percent
response rate in the KRYSTEXXA Phase 3 clinical program that
evaluated KRYSTEXXA alone, more people living with uncontrolled
gout may be able to benefit from a full course of therapy.”
Horizon is currently conducting a separate, placebo-controlled
MIRROR trial (NCT03994731) evaluating the use of KRYSTEXXA and
methotrexate. The trial, with 135 randomized patients, is designed
to enable the potential for submission of results to the U.S. Food
and Drug Administration (FDA) for update to the label.
In addition, Horizon is planning to evaluate the impact of
administering KRYSTEXXA over a shorter infusion duration. The
initial proof-of-concept work will begin mid-2020. Currently,
KRYSTEXXA is infused over a two-hour or longer timeframe. A shorter
infusion duration could meaningfully improve the experience and
convenience for patients, physicians and sites of care.
About KRYSTEXXA INDICATIONS AND USAGE
KRYSTEXXA® (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 INFORMATION WARNING: 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
METHEMOGLOBINEMIA
Patients 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 FLARES
An 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 FAILURE
KRYSTEXXA 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 REACTIONS
The 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.
Please see Full Prescribing Information and Medication Guide
for more information.
About Horizon
Horizon is focused on researching, developing and
commercializing medicines that address critical needs for people
impacted by rare and rheumatic diseases. Our pipeline is
purposeful: we apply scientific expertise and courage to bring
clinically meaningful therapies to patients. We believe science and
compassion must work together to transform lives. For more
information on how we go to incredible lengths to impact lives,
please visit www.horizontherapeutics.com, follow us @HorizonNews on
Twitter, like us on Facebook or explore career opportunities on
LinkedIn.
Forward Looking Statements
This press release contains forward-looking statements,
including statements regarding the potential benefits of combining
methotrexate treatment with KRYSTEXXA, timing and plans for future
development efforts and potential regulatory submissions. These
forward-looking statements are based on management's expectations
and assumptions as of the date of this press release and actual
results may differ materially from those in these forward-looking
statements as a result of various factors. These factors include,
but are not limited to, risks regarding whether results of the
placebo-controlled MIRROR trial will be consistent with results of
prior trials or Horizon’s expectations, and the risks associated
with clinical development of drug candidates. For a further
description of these and other risks facing Horizon, please see the
risk factors described in Horizon’s filings with the United States
Securities and Exchange Commission, including those factors
discussed under the caption “Risk Factors” in those filings.
Forward-looking statements speak only as of the date of this press
release and Horizon undertakes no obligation to update or revise
these statements, except as may be required by law.
References
- Pretreatment and co-administration with methotrexate improved
durability of pegloticase response: a prospective, observational,
proof-of-concept, case series. Poster presented at the 2019 Annual
European Congress of Rheumatology (EULAR), Madrid, Spain; June
12-15, 2019
- Subcutaneous or oral methotrexate exposure and response to
pegloticase in uncontrolled gout patients in a community
rheumatology practice. Poster presented at the 2019 Annual
Scientific Meeting of the American College of Rheumatology
(ACR/ARP), Atlanta, GA, USA; November 8 – 13, 2019.
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Tina Ventura Senior Vice President, Investor Relations
Investor-relations@horizontherapeutics.com
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media@horizontherapeutics.com
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