New Data Offers Insights on Treatment with KRYSTEXXA® (pegloticase injection) Among Kidney Transplant Patients for the Management of Uncontrolled Gout

— Initial findings from PROTECT study presented during American Society of Nephrology (ASN) Kidney Week 2020 —

— Horizon to host an online discussion with the primary investigator for PROTECT on Oct. 27 at 7 p.m. ET —

DUBLIN–(BUSINESS WIRE)–Horizon Therapeutics plc (Nasdaq: HZNP) today announced the presentation of new research from the PROspective sTudy of pEglotiCase in Transplant patients (PROTECT) trial supporting the use of KRYSTEXXA (pegloticase injection) for people who are living with chronic gout refractory to conventional therapies (also known as uncontrolled gout) and have undergone a kidney transplant. These data are being presented as part of this year’s American Society of Nephrology (ASN) Kidney Week, Oct. 22-25, 2020.

There is a strong correlation between gout and chronic kidney disease.¹ Reduced kidney function may hinder effective clearance of urate-lowering therapies,² creating additional complexities in managing both diseases. Further, evidence indicates gout is more common, and often more severe, among those who have undergone kidney transplants,³ with some data showing prevalence more than 10-fold higher than non-transplant patients.⁴

“We recognize the importance of defining gout management strategies that will not compromise kidney function or transplantation, and have focused our research on delivering new insights that can help inform nephrologists as they work to provide effective care for their patients,” said Paul Peloso, M.D., M.Sc., vice president and therapeutic area head, rheumatology, Horizon. “The unique mechanism of action of KRYSTEXXA in uncontrolled gout provides an opportunity for clinicians to address elevated uric acid levels in patients with decreased kidney function.”

(Read more…)

Pegloticase for Uncontrolled Gout in Kidney Transplant Recipients: Early Data Report of a Multicenter, Open-Label, Efficacy and Safety Study (PO2481)

Initial findings have been released from the ongoing PROTECT trial (NCT04087720),⁵ which is evaluating the safety and efficacy of KRYSTEXXA among individuals who have received a kidney transplant within the past year and are living with uncontrolled gout [defined as serum uric acid (sUA) ≥7 mg/dL and inability to maintain sUA < 6 mg/dL, intolerance of or contraindication to urate-lowering therapies, as well as either tophi, chronic gouty arthritis, and/or at least two flares in the past year]. Participants are receiving KRYSTEXXA (8 mg once every two weeks for 24 weeks) to determine response rate during Month 6 (response defined as sUA <6 mg/dL for at least 80 percent of the time).

Of the 15 patients enrolled in the trial,⁵ five patients have completed treatment with substantial and sustained reductions in sUA throughout treatment and eight patients are continuing to receive treatment. One patient stopped receiving KRYSTEXXA per monitoring protocols and one patient discontinued treatment and terminated participation early in the study over concerns of COVID-19.

“Strategies to effectively manage uncontrolled gout within the vulnerable post-transplant population are important given medications to prevent organ rejection can contribute to increased uric acid levels and lead to higher rates of uncontrolled gout,” said Abdul Abdellatif, M.D., F.A.S.N., primary investigator and assistant professor, Baylor College of Medicine. “Early data of this ongoing clinical trial are encouraging and suggest KRYSTEXXA is safe and effective for treating uncontrolled gout in this very sensitive transplant population without compromising kidney function.”

Horizon will host an online discussion on Oct. 27 at 7 p.m. ET about data from the PROTECT clinical trial featuring Abdul Abdellatif, M.D., F.A.S.N., primary investigator and assistant professor, Baylor College of Medicine, and moderated by Brad Marder, M.D., Horizon medical director.

Additional studies presented at ASN include:

• A USRDS database study on the use of pegloticase in patients undergoing dialysis (PO1166)
  
  Understanding the experience of people with chronic kidney disease and uncontrolled gout is vital to defining new therapeutic approaches that can benefit this vulnerable population. This United States Renal Data System (USRDS) study was conducted to better understand how KRYSTEXXA is applied in real-world care for people who receive dialysis for advanced renal disease. Data were collected from USRDS records of 136 patients who received KRYSTEXXA between 2012 and 2017 prior to or following end stage renal disease (ESRD) to evaluate demographics, comorbidities, dialysis type, number of KRYSTEXXA infusions, and time between infusions.

  The real-world usage analysis illustrates that KRYSTEXXA is effectively employed and well-tolerated among dialysis patients. Of the 136 patients reviewed, 77 patients received KRYSTEXXA following ERSD and 42 of the 77 patients underwent routine dialysis while receiving KRYSTEXXA. The 42 patients received an average of 9.5 infusions at a treatment schedule consistent with labeling guidelines, with a 14-day median time between doses. The majority were white (55 percent), male (76 percent) and averaged 54 years of age; all adult age groups were represented (18-44 years: 29 percent, 45-64 years: 54 percent, ≥65 years: 17 percent). Hypertension (81 percent), diabetes (45 percent) and congestive heart failure (24 percent) were the most commonly reported comorbidities. Seven patients were donor kidney recipients, and more patients were undergoing hemodialysis (76 percent) than peritoneal dialysis (24 patients).

• Treatment Response in Patients with Uncontrolled Gout Co-treated with Pegloticase and Leflunomide (PUB035)
  
  Presented as an online abstract, this retrospective in-practice case series showed 70 percent (7 out of 10 patients) achieved a complete response when co-treated with KRYSTEXXA and leflunomide. Three patients discontinued or were lost to follow-up.

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 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 and follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding the potential benefits of KRYSTEXXA for kidney transplant patients. 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 further results of the PROTECT clinical trial will be consistent with preliminary results or Horizon’s expectations and the risks associated with clinical development. 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

1. Singh JA, Cleveland JD. Gout is associated with a higher risk of chronic renal disease in older adults: a retrospective cohort study of U.S. Medicare population. BMC Nephrol. 2019;20(1):93.
2. Vargas-Santos AB, Neogi T. Management of gout and hyperuricemia in CKD. Am J Kidney Dis. 2017;70(3):422-439.
3. Brigham MD, Radeck LP, Mendonca CM, et al. Gout severity in recipients of kidney transplant. Transplantation Proceedings. 2019;51(6):1816–1821.
4. Brigham MD, Milgroom A, Lenco MO, et al. Prevalence of gout in the surviving United States solid organ transplantation population. Transplantation Proceedings. 2019;51(10):3449–3455.
5. National Institute of Health. Study of Pegloticase in Patients with Uncontrolled Gout Who Have Had a Kidney Transplant (PROTECT). https://clinicaltrials.gov/ct2/show/NCT04087720. Accessed Oct. 15, 2020.

 

Contacts

Tina Ventura
Senior Vice President, Investor Relations

[email protected]

Ruth Venning
Executive Director, Investor Relations

[email protected]

U.S. Media Contact:
Amanda Phraner
Director, Public Relations and Social Media

[email protected]

Ireland Media Contact:
Gordon MRM
Ray Gordon

[email protected]