Horizon Therapeutics plc Initiates ADVANCE Trial Evaluating KRYSTEXXA® (pegloticase injection) with Methotrexate for People Who Previously Developed Anti-Drug Antibodies on KRYSTEXXA Monotherapy

Rhea-AI Summary

Horizon Therapeutics plc (Nasdaq: HZNP) announced the enrollment of the first patient in the ADVANCE trial, which examines the use of KRYSTEXXA (pegloticase injection) combined with methotrexate for patients with uncontrolled gout who did not respond to KRYSTEXXA alone. This open-label trial aims to enroll 30 patients and has a primary endpoint of maintaining serum uric acid levels below 6 mg/dL for at least 80% of Month 6. The safety and efficacy of this combined treatment are yet to be established by health authorities.

Positive

• Enrollment of the first patient in the ADVANCE trial indicates progress in developing new treatment options for uncontrolled gout.
• The trial aims to assess a combination therapy approach, which may enhance treatment efficacy for patients previously unresponsive to KRYSTEXXA monotherapy.

Negative

• The safety and efficacy of KRYSTEXXA with methotrexate has not been evaluated or approved by health authorities.
• The trial's small size of 30 patients may limit the generalizability of the findings.

Horizon Therapeutics plc (Nasdaq: HZNP) today announced the first patient has enrolled in the ADVANCE trial evaluating the concomitant use of KRYSTEXXA (pegloticase injection) with methotrexate for people with uncontrolled gout who were not able to achieve a complete response when previously treated with KRYSTEXXA monotherapy.

For people with chronic gout refractory to conventional therapies (uncontrolled gout), KRYSTEXXA offers a unique mechanism of action that converts urate into allantoin which can more easily and efficiently be excreted by the kidneys.¹ Similar to other biologic medicines, patients on KRYSTEXXA monotherapy can develop anti-drug antibodies that prevent them from completing a full course of therapy. Increasingly, immunomodulating therapies, such as methotrexate, have been employed to help reduce the development of anti-drug antibodies.² With this understanding, the ADVANCE trial will evaluate if repeating the course of KRYSTEXXA therapy with an immunomodulator as co-therapy may help more patients, who previously lost response with KRYSTEXXA monotherapy, to achieve a complete response.

"We are acutely aware of the impact systemic urate deposition has on patients, notably the permanent damage to joints, bone erosion and the increased risk of kidney disease,” said Orrin Troum, M.D., clinical professor of medicine and voluntary faculty member in the Division of Rheumatology at the Keck School of Medicine, University of Southern California and rheumatologist with Providence Saint John's Health Center in Santa Monica, California. “To help maximize treatment options, the ADVANCE trial incorporates insights from current rheumatology practice.”

ADVANCE is an open-label trial designed to evaluate the efficacy and safety of KRYSTEXXA used with methotrexate for people with uncontrolled gout who previously lost response when treated with KRYSTEXXA monotherapy. The trial will enroll 30 patients. The primary endpoint is the response rate, defined as a serum uric acid level of <6 mg/dL for at least 80 percent of the time during Month 6. Participants will receive 8 mg infusions of KRYSTEXXA every two weeks, along with a weekly course of 15 or 25 mg (depending on their renal function) of methotrexate administered subcutaneously, after a methotrexate run-in period, which provides a preferred pharmacokinetics profile for this trial.³ The safety and efficacy of KRYSTEXXA co-prescribed with methotrexate has not been evaluated or approved by any health authority.

“As the impact of systemic urate deposition becomes better understood, having options to treat and re-treat patients is increasingly important for patients with uncontrolled gout and systemic urate deposition,” said Theresa Podrebarac M.D., MSc., senior vice president, clinical development, Horizon. “We believe a substantial portion of patients who were not complete responders to treatment with KRYSTEXXA monotherapy could be good candidates for this approach and that insights from this trial could help shape clinical care for those with uncontrolled gout.”

Additional details on the study sites and protocol can be found at www.clinicaltrials.gov (NCT04772313).

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 fail

FAQ

What is the ADVANCE trial by Horizon Therapeutics for KRYSTEXXA?

The ADVANCE trial evaluates the safety and efficacy of KRYSTEXXA combined with methotrexate for uncontrolled gout patients who previously did not respond to KRYSTEXXA alone.

When did patient enrollment begin for the ADVANCE trial?

The first patient has been enrolled in the ADVANCE trial announced by Horizon Therapeutics.

What are the primary goals of the ADVANCE trial for HZNP?

The primary goal is to achieve a serum uric acid level of <6 mg/dL for at least 80% of the time during Month 6 in trial participants.

What is the significance of the KRYSTEXXA and methotrexate combination therapy?

This combination aims to enhance the treatment response for patients who did not achieve results with KRYSTEXXA monotherapy, potentially providing a new option for those with uncontrolled gout.

How many patients will participate in the ADVANCE trial?

The ADVANCE trial is designed to enroll 30 patients.