Termination of Ultragenyx’s UX053 Phase I/II study is a minor setback for mRNA therapeutics: GlobalData

Ultragenyx has terminated its Phase I/II trial for pipeline candidate UX053, a non-vaccine mRNA therapeutic for glycogen storage disease type III, also known as Cori’s disease. The study was terminated due to reasons unrelated to safety concerns, although the specific rationale has not been disclosed by the biopharma company. mRNA therapeutics hold a lot of promise because of the technology’s potential applicability to a wide range of disorders, says GlobalData.

According to GlobalData, UX053 was one of five non-vaccine mRNA therapeutics in clinical trial development. The other four are all currently in Phase I/II under Moderna, BioNTech, and Omega Therapeutics. These pharma companies are exploring non-vaccine mRNA therapeutics for rare diseases and oncological disorders.

Sarah Bundra, Analyst at GlobalData, comments, “Other rare indications that are being explored in non-vaccine mRNA clinical trial development include methylmalonic acidemia and propionic acidemia. However, proving the efficacy of mRNA therapeutics could be tricky, especially for rare diseases in which participant recruitment is difficult.”

UX053 is an antisense oligonucleotide to be intravenously administered. Participants in Phase I/II trial received a single peripheral intravenous infusion of UX053. After completion of a 90-day follow-up period, study participants could then elect to enter the open-label repeat-dose cohort to receive a dose of UX053 every four weeks for four doses. Cori’s disease is an inherited rare disorder caused by the buildup of glycogen in the body’s cells, impairing organ and tissue function throughout the body but especially in the liver and muscles.

Sarah Bundra, Analyst at GlobalData, comments, “R&D in the mRNA therapeutic space has expanded significantly since mRNA technology proved instrumental in fighting the COVID-19 pandemic. Now, pharmaceutical companies are exploring mRNA technology’s potential in other disease areas.”

mRNA therapeutics involve the in vitro transcribed (IVT) mRNA into a target cell, where cellular machinery translates the mRNA into a functional protein. This allows for the transient expression of proteins that are absent, dysfunctional, or have been suppressed in various diseases.

Bundra concludes, “mRNA therapeutics are novel because they can be used for precise and individualised therapy based on a patient’s specific DNA. Hopefully, BioNTech, Omega Therapeutics, and Moderna’s non-vaccine mRNA therapeutics do not follow Ultragenyx’s UX053 with an early clinical trial termination.”