A minority of patients taking Ultragenyx Pharmaceutical’s Wilson disease gene therapy UX701 have come off standard-of-care drugs, leading the biotech to enroll a new cohort on a tweaked regimen designed to dial up the efficacy.
Wilson patients take chelation therapy drugs such as Bausch Health’s Cuprimine and Orphalan’s Cuvrior to remove the excess copper that drives the disease. However, treatment is a lifelong process, and efforts to bring new drugs to market have faltered. AstraZeneca dropped a drug candidate once considered to be worth $855 million after failing to show copper was eliminated from the body, not just redistributed.
An effective gene therapy could free patients from the need to take chelation therapy drugs. Ultragenyx shared an update on its work to deliver those benefits after the markets closed Thursday, when the biotech provided an update on the first stage of its pivotal phase 1/2/3 Cyprus2+ study.
The first stage enrolled 15 patients into three sequential dosing cohorts and tracked them for at least 24 weeks. As of the cutoff in August, six patients had completely tapered off the standard-of-care chelators or zinc therapy. A seventh person had begun to taper as of the cutoff. Non-ceruloplasmin-bound copper had stabilized to normal, healthy levels in patients who had come off standard therapies.
Talking on an earnings call at the start of August, Ultragenyx CEO Emil Kakkis, M.D., Ph.D., said an effective Wilson gene therapy would need to get patients off standard of care and keep free copper and urinary copper excretion at a level that indicates they are detoxifying copper through the proper pathway.
As well as enabling people to taper, Kakkis wanted to “see some significant improvement in the majority of patients in copper distribution, that is ceruloplasmin-copper levels, which are generally very low” in the targeted patient population. Ultragenyx said “some patients” in the clinical trial had “increases in ceruloplasmin-copper activity consistent with improved ATP7b function.”
The efficacy data, coupled to absence of unexpected treatment-emergent adverse events and significant immunologic safety events, led the biotech to plan a protocol amendment intended to boost efficacy to the point most people come off standard therapy. Ultragenyx said it will “moderately” increase the dose and optimize the immunomodulation regimen.
Data on the new cohort will inform the second part of the study, when Ultragenyx will randomize people to receive placebo or the UX701 dose that looks most promising in stage one. The biotech will assess the safety and efficacy of UX701 after 52 weeks in the planned placebo-controlled portion of the study.