Horizon Therapeutics Announces First Subject Dosed in Phase 1 Trial Evaluating HZN-457 for the Treatment of Gout

Horizon Therapeutics has announced the first subject has been dosed in a Phase 1 randomized, placebo-controlled trial to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of its development-stage medicine HZN-457 for the treatment of Gout.  HZN-457 is a small interfering RNA candidate designed to treat gout by silencing liver xanthine dehydrogenase. The development of HZN-457 is part of a global collaboration and license agreement that the Company entered in 2021 with Arrowhead Pharmaceuticals.

Gout is a serious and painful form of inflammatory arthritis that is caused by excess uric acid. In the United States, there are more than 9 million gout patients and approximately a third are treated with oral urate-lowering therapies. However, a meaningful portion of those patients do not respond sufficiently and continue to experience painful and debilitating gout symptoms. High uric acid levels, if left untreated or undertreated, can lead to acute and persistent inflammatory arthritis, bone and joint damage, exacerbate comorbidities, and severely impact patients’ lives. Preclinical studies suggest that HZN-457 has the potential to maintain lower uric acid levels and offer several benefits above standard of care for the treatment of gout.

Up to 56 healthy volunteers are expected to be enrolled sequentially into ascending dose cohorts and administered HZN-457 subcutaneously as a single dose. The primary endpoint is safety and tolerability. Secondary endpoints include the assessment of plasma and urine pharmacokinetic parameters and changes from baseline in uric acid levels.

“As a clinical and commercial leader in gout, Horizon understands the critical need to develop innovative approaches and advance novel treatments to reach more patients who live with this disease,” said Elizabeth Thompson, executive vice president, research and development, Horizon Therapeutics. “The HZN-457 Phase 1 clinical trial marks an important milestone for Horizon to advance our research and development in this space, fostered by our partnership with Arrowhead.”