Novel Therapy Improves Neurologic and Functional Outcomes in Children with Ataxia-Telangiectasia

People with ataxia-telangiectasia (A-T) treated with EryDex (dexamethasone sodium phosphate encapsulated in autologous erythrocytes; Quince Therapeutics, South San Francisco, CA) showed reductions in neurologic symptoms, according to results of the phase 3 ATTeST clinical trial (NCT02770807), published in The Lancet Neurology.

ATTeST was a randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of EryDex at 2 dose levels vs placebo in treating neurologic symptoms of people with A-T. The study included 175 participants aged >6 years from 22 institutions across 12 countries. The primary efficacy measure of the study was reduction in neurologic symptoms as measured by change in modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to 6 months.

• There was a change of -1.40 in mICARs at 6 months in participants treated with high-dose EryDex, which was not statistically significant (nominal P=.077).
• Participants in the per-protocol population showed a change of -2.2 in mICARS (nominal P=.019).
• 35% of participants in the modified intent-to-treat (mITT) population were excluded from the per-protocol population, primarily due to late- or missed-doses attributable to travel difficulties and disruptions caused by the COVID-19 pandemic.
• Participants in a pre-specific subgroup for those aged 6 to 9 years receiving high-dose EryDex showed a change of -2.8 (nominal P=.019) and -4.4 (nominal P=.002) in mICARS in the mITT and per-protocol populations, respectively.
• No serious safety concerns typically associated with chronic corticosteroid use were observed after 6 months of treatment with EryDex.

“Natural history studies have shown that children between age six and 10 with classic A-T experience rapid clinical decline, after neurological symptoms worsen and patients with A-T frequently become wheelchair-bound by adolescence,” said Dr. William Whitehouse, Honorary Clinical Associate Professor of the School of Medicine at the University of Nottingham and Consultant Pediatric Neurologist at Nottingham Children’s Hospital, Nottingham University Hospitals NHS Trust. “The differential response in mICARS score by age seen in subgroup analyses from the ATTeST study emphasizes the need to stratify future A-T clinical trials by age.”

A-T is a rare inherited autosomal recessive neurodegenerative and immunodeficiency disorder caused by mutations in the ATM gene, which typically has an onset in early childhood. Neurologic decline accelerates between ages 6 and 10, associated with movement difficulty, speech difficulty, and oculomotor apraxia.