-- Horizon data at American College of
Rheumatology Annual Meeting also cite the need for vigilance in
treating gout among kidney transplant recipients --
Horizon Therapeutics plc (Nasdaq: HZNP) today announced the
presentation of a patient case series at the American College of
Rheumatology (ACR) Annual Meeting illustrating that the addition of
methotrexate to a course of therapy with KRYSTEXXA® (pegloticase
injection) may help more people with chronic gout refractory to
conventional therapies – also known as uncontrolled gout – achieve
response to treatment. In addition, Horizon will present data
describing the inflammatory impact of uric acid on other organs,
including the liver and kidney.
KRYSTEXXA has demonstrated rapid reduction in the serum uric
acid level for people with uncontrolled gout; however, as with any
biologic, the immune system can sometimes react to the therapeutic
proteins, hindering a complete response. Immunomodulators, such as
methotrexate, are often co-prescribed with biologics to help reduce
this reaction.
The case series presented by John A. Albert, M.D. details his
in-practice experience for 10 adult patients with uncontrolled gout
who received KRYSTEXXA during or after treatment with methotrexate
(either oral or subcutaneous). Methotrexate exposure varied (most
received 25 mg of methotrexate subcutaneously every week and nine
of the 10 patients started methotrexate prior to receiving
KRYSTEXXA). Eight of the 10 patients were complete responders at 24
weeks of therapy. Two patients ceased therapy, one due to loss of
response and a mild infusion reaction, and the other due to
methotrexate injection-related issues. Treatment was well tolerated
for the duration of therapy. Given the importance of this clinical
concept, Horizon assisted with the analysis and compilation of the
case series. The co-prescription of KRYSTEXXA and methotrexate is
investigational and its safety and efficacy have not been
established. (Subcutaneous or oral methotrexate exposure and
response to pegloticase in uncontrolled gout patients in a
community rheumatology practice, Abstract 1236)
“Despite gout being the most common form of inflammatory
arthritis, it is often not treated with urgency that reflects the
impact on patients and its serious, chronic and systemic nature,”
said John A. Albert, M.D., Rheumatic Disease Center, Glendale, WI.
“In order to address the impact of gout for patients like mine, it
is important we quickly and effectively decrease the uric acid
burden. Adding methotrexate to KRYSTEXXA treatment for patients
with uncontrolled gout employs a commonly used immunomodulation
strategy by rheumatologists to minimize the immune response and
strives to help more patients benefit from a full course of
therapy. This case series demonstrates the significant improvement
in response rate which can be achieved through this treatment
strategy.”
These in-practice insights expand upon earlier clinical evidence
of the immunomodulation strategy from independent investigators,
presented during the ACR Annual Meeting in 20181 as well as the
Annual European Congress of Rheumatology (EULAR) earlier in 2019.2
Horizon is also evaluating the use of methotrexate to increase the
response rate with KRYSTEXXA in its immunomodulation trials, the
small MIRROR open-label pivotal study initiated in 2018, and the
larger MIRROR registrational clinical trial, which was initiated
earlier this year.
Additional presentations deliver new insights on the systemic,
inflammatory aspects of uric acid and its effects on multiple organ
systems.
- Inflammatory effects of uric acid on liver health in people
living with gout:
- Improvement in Hepatic Fibrosis Estimated by Fibrosis-4 (FIB-4)
Index in Subjects with Chronic Refractory Gout Treated with
Pegloticase, Abstract 1231 Prior research has described the link
between hyperuricemia and non-alcoholic fatty liver disease
(NAFLD). This study evaluates the hypothesis that lowering uric
acid levels with KRYSTEXXA may improve the course of NAFLD for
people living with gout.
- The complex correlation between kidney transplantation and
gout:
- Renal Transplant Complications in Patients with and without
Gout, Abstract 335 Gout is a known co-morbidity among people who
have undergone renal transplantation. This evaluation has assessed
whether the presence of gout contributes to greater complications
after transplant, with the goal of elevating awareness of prompt
gout screening and management strategies within this vulnerable
population.
- Incident Gout after Renal Transplantation in Gout-naïve
Patients: Large Database Analysis, Abstract 332 While evidence has
described a clear link between renal transplantation and gout,
important factors remain unclear about this link, such as the
frequency of this occurrence and the timing of gout after renal
transplant. This study quantifies the incidence of gout in
gout-naïve patients undergoing renal transplantation, offering
important insights to physicians to help properly identify and
intervene to control the disease.
“Our research efforts are illustrating important indicators of
the multi-organ impact of gout, particularly in the liver and
kidneys, where uncontrolled gout can contribute to long-term health
consequences,” said Jeffrey D. Kent, M.D., FACG, FACP, executive
vice president, medical affairs and outcomes research, Horizon.
“Combined with other insights at the ACR meeting, this research
highlights the need for clinicians to look holistically at their
care strategy for people with gout to ensure the disease is well
controlled through appropriate treatment regimens.”
About Uncontrolled Gout
Gout is a chronic, progressive inflammatory form of arthritis
that is caused by excess uric acid in the body and needs to be
managed aggressively.3 Over time uric acid can build up and form
deposits, called tophi, inside the body and joints, which can have
harmful effects including causing damage to the underlying bone.
Patients with uncontrolled gout continue to have abnormally high
levels of uric acid and continued symptoms of gout despite the use
of conventional therapies.4 KRYSTEXXA is the only biologic approved
by the U.S. Food and Drug Administration (FDA) for the treatment of
uncontrolled gout in adult patients.
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 KRYSTEXXA,
including in combination with methotrexate and expectations
regarding the MIRROR clinical trial. 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 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 2018 Annual
Scientific Meeting of the American College of Rheumatology (ACR),
Chicago, IL, USA; October 19–24, 2018.
- 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.
- Keuhn B. Chronic Disease Approaches Needed to Curb Gout’s
Growing Burden. Journal of the American Medical Association.
2018;319(13):1308-1309.
- Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia
in the US general population: the National Health and Nutrition
Examination Survey 2007-2008. Arthritis Rheum.
2011;63(10):3136-3141.
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Investor-relations@horizontherapeutics.com
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Director, Public Relations and Social Media
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