New Data Being Presented at American College of Rheumatology Convergence 2021 Highlight Horizon’s Commitment to Improving Outcomes for People Living with Uncontrolled Gout

-- Survey results of practicing rheumatologists suggest presence of negative gout stigma in causality and management of gout --

-- New analyses of real-world experience of KRYSTEXXA^® (pegloticase injection) adds to the body of data supporting the use of concomitant immunomodulation --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced presentations on results from a new survey of practicing rheumatologists suggesting the presence of negative gout stigma surrounding causality and management of gout. In addition, the largest in-practice analysis to-date showing the use of KRYSTEXXA (pegloticase injection) with immunomodulation may impact treatment response rates for people living with chronic gout refractory to conventional therapies, also known as uncontrolled gout will be presented at the American College of Rheumatology Convergence 2021, Nov. 5-9, 2021.

Key gout presentations include:

Gout Stigma: Investigating the Existence of Gout Stigma and Its Impact on Patient Perceptions and Treatment Decisions. Results from a new online survey of 106 practicing rheumatologists show how a perceived stigma associated with gout can influence physicians’ perceptions of patient illness and their resulting treatment decisions. Rheumatologists were surveyed on their perceptions, experiences and recommendations for patients with controlled gout, uncontrolled gout and rheumatoid arthritis (RA).

Key findings include:

• A higher level of personal responsibility was perceived for gout than for RA, and patients with gout were thought to be less likely to comply with prescribed treatment regimens.
• Patient personal behavior, diet, body mass index (BMI) and lack of treatment adherence were perceived as greater contributing factors to disease in gout patients than in RA patients (p<0.01).
• Change in diet, increased exercise and weight loss were perceived as more beneficial for managing gout than for managing RA (p<0.01), with biological pharmacological treatment perceived as less beneficial to patients with gout than to those with RA.

“Based on these survey results, despite good intentions, rheumatologists’ causal beliefs and illness perceptions of gout reflect pervasive negative stereotypes, which have critical implications for how physicians interact with patients,” said N. Lawrence Edwards, M.D., lead author on the study and professor of medicine, Division of Clinical Immunology at the University of Florida in Gainesville and chairman of the Gout Education Society. “Education on the stigma surrounding gout, even among rheumatology specialists, is crucial to reinforce the serious and systemic impact of this disease, and the long-term consequences if not properly treated. By recognizing and addressing the potential bias in gout treatment decisions, we can improve clinical care and, subsequently, patient outcomes.”

Key KRYSTEXXA presentations include:

Effectiveness and Safety of Pegloticase with Concomitant Immunomodulatory Therapy. A retrospective registry analysis evaluated KRYSTEXXA persistence and adverse events associated with concomitant immunomodulation in 700 patients initiating KRYSTEXXA. The analysis assessed outcomes among two segments of treated patients: those who received an immunomodulator within 60 days of beginning KRYSTEXXA (124 patients), and those who did not receive an immunomodulator (576 patients). Efficacy analysis compared the proportion of patients who achieved target serum uric acid (sUA) level (sUA ≤6mg/dL). Safety analysis included lab abnormalities (such as low white blood cell, platelet or hematocrit counts or elevated ALT or AST levels) among KRYSTEXXA users within 180 days from the start of treatment.

The findings indicated that the concomitant use of KRYSTEXXA with an immunomodulator may help improve persistence to therapy. In total, approximately 90% of the evaluated population met the sUA treatment target, and those who received immunomodulation after starting on KRYSTEXXA were less likely to discontinue their treatment compared to non-users (hazard ratio, 0.57). Lab abnormalities were uncommon among KRYSTEXXA users (<5%) and were not higher among those who also received immunomodulatory therapy, indicating that the addition of immunomodulation to KRYSTEXXA was well tolerated in this uncontrolled gout population.

Concomitant Immunomodulation and Pegloticase Therapy: Experiences with a Variety of Immunomodulatory Agents in Two Community Rheumatology Practices. A separate chart review presented the clinical experiences among two rheumatology practices where an immunomodulator is routinely prescribed for individuals receiving KRYSTEXXA. A total of 34 patients with uncontrolled gout who received KRYSTEXXA with an immunomodulator prior to or with the first infusion were evaluated. Analyses included the proportion of patients who were considered to be responders (defined as ≥12 KRYSTEXXA infusions and sUA <6 mg/dL at Infusion 12) as well as change in estimated glomerular filtration rate (eGFR) and change in stage of chronic kidney disease (CKD). Immunomodulators included subcutaneous methotrexate (20 patients), oral methotrexate (9 patients), oral mycophenolate mofetil (3 patients) and oral azathioprine (2 patients). Of the 34 patients, 28 reached 12 infusions with six remaining on treatment having not reached Infusion 12 at time of data analyses. Nearly 90% (25 of 28) of participants achieved a treatment response, with a slight increase in the mean eGFR during therapy. The CKD stage remained stable or improved in 85% of patients (29 of 34). No new safety concerns were identified.

“Research continues to illustrate the serious, long-term, systemic consequences of uncontrolled gout and draws attention to the need to urgently address the burden of disease,” said Jeffrey D. Kent, M.D., FACG, FACP, executive vice president, medical affairs and outcomes research, Horizon. “We remain committed to advancing understanding of this disease and reimagining treatment approaches to improve patient outcomes. Results from additional in-practice and clinical trial data continue to reinforce published literature and the paradigm shift of using an immunomodulator with KRYSTEXXA to treat uncontrolled gout."

Additional presentations at ACR supported by Horizon include:

• Assessing the Extent of Lumbosacral Spinal Urate Deposition in Patients with Tophaceous and Nontophaceous Gout Compared with Non-Gout Controls Using Dual-Energy CT (DECT) (0467)
  
  This study used dual-energy computed tomography (DECT) imaging to evaluate the extent of monosodium urate (MSU) deposition in the lumbosacral spines of patients with gout (with and without tophi), compared to patients without gout. Gout patients were found to have larger MSU volumes than the control group, and tophaceous patients had numerically greater MSU deposition compared with nontophaceous patients.

• Disappearing Digits: A National Retrospective Matched Cohort Study Examining the Risk of Lower Extremity Amputation in Gout (0663)
  
  Using national Veterans Health Administrative (VHA) data from January 1999 to July 2015, this retrospective matched cohort study identified that patients with gout are at a 33% increased risk for undergoing lower extremity amputation, with an even higher risk for below-the-knee amputations. This risk is independent of other comorbidities that have been associated with lower extremity amputation including diabetes.

• Early-Onset Gout (EOG) Patients are an Important and Recalcitrant Phenotype Warranting Further Investigation: A Systematic Review (0669)
  
  A systematic review was conducted to examine publications and abstracts providing insight into the overall profile of early-onset gout (EOG) patients, typically defined as patients diagnosed with gout under the age of 40 years, compared to common gout (CG) patients. Included references produced consistent results that EOG patients present with more severe joint disease compared to CG patients and are less likely to achieve target serum urate level (sUA < 6mg/dL). In addition, the literature as a whole suggested that EOG patients may require earlier and more aggressive urate-lowering therapy to adequately achieve target sUA.

• Economic and Healthcare Resource Use Burden of Systemic Sclerosis (0143)
  
  This retrospective cohort comparison was performed using a claims dataset capturing beneficiary-level claims between 2015 and 2019 to evaluate the health care resource use (HCRU) and costs of systemic sclerosis (SSc) patients prior to and immediately after diagnosis. SSc patients appear to accrue markedly greater health care costs and require more services than a matched unaffected general population. Elevated expenditures and HCRU are observed from at least two years before a confirmed SSc diagnosis with both increasing over time, a dynamic that likely reflects both the progressive, multi-system nature of SSc and the potential challenges and delays in diagnosis. Additionally, despite no proven disease-modifying therapy, SSc patients accrued substantial drug costs for therapies likely used to suppress emerging sequalae of the underlying disease. Together, these findings suggest that SSc patients pose a substantial burden on the health care system and highlight the need for early diagnosis and effective therapies.

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 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 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, please visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

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