• New data illustrate impact of KRYSTEXXA^® (pegloticase) injection with methotrexate to improve patient outcomes and clinical measures for uncontrolled gout 

DUBLIN / May 31, 2023 / Business Wire / Horizon Therapeutics plc (Nasdaq: HZNP) today announced new analyses from the MIRROR randomized controlled trial of KRYSTEXXA^® (pegloticase) injection with methotrexate show a multi-faceted impact when treating adults living with chronic gout refractory to oral therapy, or uncontrolled gout. Presentations are part of expert discussions at the EULAR European Congress of Rheumatology, May 31 - June 3, 2023, in Milan.

Data presented from Horizon’s MIRROR randomized controlled trial (RCT), which evaluated KRYSTEXXA in combination with methotrexate for uncontrolled gout, provide further evidence of the impact of therapy on patient-reported outcomes (PROs), urate depletion and bone remodeling.

“Uncontrolled gout is far more painful and dangerous than most people know,” said Brian LaMoreaux, M.D., M.S., senior medical director, Horizon. “This disease can erode joints and bones, impact vital organs and contribute to serious health conditions. What is demonstrated in the new data from the MIRROR RCT is that by sustaining a reduced serum urate level it is possible to deliver progressive meaningful improvements.”

Key KRYSTEXXA Presentations

• PROs and gout-related clinical measures captured in the MIRROR RCT included changes from baseline to week 52 in Health Assessment Questionnaire (HAQ) indices (Disability Index, Pain and Health), Physician Global Assessment of Gout (PhGA), and tender or swollen joint counts (TJC/SJC). All quality-of-life measures and gout-related clinical measures progressively improved during treatment and TJC/SJC markedly declined. Participants who received KRYSTEXXA with methotrexate experienced greater improvements in HAQ-Pain and HAQ-Health scores after 52 weeks of therapy than those who received KRYSTEXXA with placebo, potentially because of the higher urate-lowering response rate seen with the co-therapy approach. Quality of life and clinical gout assessment changes in uncontrolled gout patients undergoing pegloticase therapy as part of the MIRROR randomized controlled trial (POS0513)

• The MIRROR RCT used dual-energy computed tomography (DECT) imaging to visualize monosodium urate (MSU) crystal deposits, which have been shown to be associated with gout-related bone erosions. Analyses of DECT findings showed rapid and near-complete depletion of MSU crystal deposits within one year of initiating KRYSTEXXA treatment (94% volume reduction in nine imaged regions of six patients who received KRYSTEXXA with methotrexate; 90% volume reductions in five imaged regions of two patients who received KRYSTEXXA with placebo). Imaging findings also indicated that bone remodeling may be possible following depletion of MSU deposits. Evidence of bone remodeling was seen in 69% (29/42) of evaluated erosions (9/12 imaged regions). Of the 29 erosions with remodeling, all had a decrease in size (mean 7% volume reduction change at week 52), with new bone formation also observed in some erosions. Bone erosion remodeling after depletion of monosodium urate deposition with intensive urate-lowering with pegloticase in patients with uncontrolled gout: MIRROR RCT dual-energy CT findings (POS0514)

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory 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, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

About KRYSTEXXA

INDICATION

KRYSTEXXA^® (pegloticase) is indicated for the treatment of chronic gout in adult 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.

Limitations of Use: KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.

IMPORTANT SAFETY INFORMATION

WARNING: ANAPHYLAXIS AND INFUSION REACTIONS, G6PD DEFICIENCY ASSOCIATED HEMOLYSIS AND METHEMOGLOBINEMIA

• 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. Delayed 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 and closely monitored for anaphylaxis for an appropriate period after administration of KRYSTEXXA.
• Serum uric acid levels should be monitored prior to each infusion and treatment discontinued if levels increase to above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed.
• Patients at risk for glucose-6-phosphate dehydrogenase (G6PD) deficiency should be screened prior to starting KRYSTEXXA. Hemolysis and methemoglobinemia have been reported with KRYSTEXXA in patients with G6PD deficiency. KRYSTEXXA is contraindicated in patients with G6PD deficiency.

CONTRAINDICATIONS:

• In patients with G6PD deficiency.
• In patients with history of serious hypersensitivity reactions, including anaphylaxis, to KRYSTEXXA or any of its components.

WARNINGS AND PRECAUTIONS

Gout Flares: An increase in gout flares is frequently observed upon initiation of anti-hyperuricemic therapy, including KRYSTEXXA. 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 formally studied in patients with congestive heart failure, but some patients in the pre-marketing placebo-controlled clinical trials experienced exacerbation. Caution should be exercised in patients who have congestive heart failure and patients should be closely monitored following infusion.

ADVERSE REACTIONS

The most commonly reported adverse reactions (≥5%) are:

• KRYSTEXXA co-administration with methotrexate trial: gout flares, arthralgia, COVID-19, nausea and fatigue; KRYSTEXXA alone: gout flares, arthralgia, COVID-19, nausea, fatigue, infusion reactions, pain in extremity, hypertension and vomiting.
• KRYSTEXXA pre-marketing placebo-controlled trials: gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting.

Please see Full Prescribing Information, including Boxed Warning.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding the potential benefits of KRYSTEXXA co-administered with methotrexate for uncontrolled gout. 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 related to the adoption of co-administration of KRYSTEXXA with methotrexate for uncontrolled gout and whether future data analyses or clinical trial results will be consistent with prior clinical trials or Horizon’s expectations. 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.