Benzinga | Oct 22, 2020 10:03AM EDT

Horizon Therapeutics Highlights Will Offer Initial Findings From PROTECT Study At Kidney Week 2020

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."

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.