Ultragenyx Initiates Dosing in Second Cohort of Pivotal Phase 1/2/3 Cyprus2+ Trial for UX701 Gene Therapy in Wilson Disease Treatment
Tuesday, August 01, 2023
Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) recently announced the initiation of the second dose-escalation cohort in its pivotal Phase 1/2/3 Cyprus2+ study after completing dosing and safety review in the first cohort. The study focuses on their investigational AAV9 gene therapy, designed to treat patients with Wilson disease by delivering stable expression of the ATP7B copper transporter through a single intravenous infusion, with the aim of normalizing copper metabolism.
The first dose cohort, UX701, has been well-tolerated with no unexpected treatment-related adverse events reported as of July 11, 2023. Based on recommendations from the Data Safety Monitoring Board, the company is proceeding with dosing at a higher dose of 1.0 x 10^13 GC/kg. The enrollment in Stage 1 of the trial is expected to be completed this year, and the company plans to share initial data in the first half of 2024.
The Cyprus2+ study is designed with three stages. In Stage 1, the safety and efficacy of up to three dose levels of UX701 will be evaluated over 52 weeks, with a dose selected for further evaluation in Stage 2. The Stage 2 cohort will be randomized to receive either the selected dose of UX701 or a placebo. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard of care medication by Week 52.
Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, leading to copper accumulation in the liver and other tissues. Patients may experience hepatic, neurologic, and/or psychiatric symptoms. Current treatment options include reducing copper absorption or removing excess copper from the body using chelation therapy. However, there are still unmet needs as some patients experience clinical deterioration and severe side effects.
UX701, an investigational AAV9 gene therapy, has shown promising results in preclinical studies, normalizing copper trafficking and excretion. The U.S. FDA has granted Orphan Drug Designation to UX701.
