Abstract Details

Title Phase 2/3 Clinical Trial Results: Safety & Efficacy Results of RT001, a site-specific (C11) di-deutero synthetic homologue of linoleic acid, in Infantile Neuroaxonal Dystrophy

Topic Child Neurology and Developmental Neurology

Presentation(s) S39 - Child Neurology and Developmental Neurology (4:42 PM-4:54 PM)

Poster/Presentation
Number 007

Background Infantile neuroaxonal dystrophy (INAD), is a progressive, fatal neurogenetic disorder caused by loss of PLA2G6 enzyme activity, which leads to impaired remodeling of oxidized membrane phospholipids and to neuronal death. It has been established previously that substitution of hydrogen with deuterium at specific bis-allylic sites, as in RT001, decreases the production of lipid peroxidation products. We hypothesized that RT001 might be able to improve the course of disease in children with INAD.

Objective To test the safety and efficacy of RT001 in children with infantile neuroaxonal dystrophy, compared to a concurrent natural history study.

Design/Methods There were 19 INAD patients in the treatment study, and 36 INAD patients in the natural history study. The minimum treatment period was 1 year, and outcome measures included survival, neurological rating scales and parental assessments.

Results The primary efficacy measure, the Modified Ashworth Spasticity Scale using the Combined Assessment of Function and Survival (CAFS) analysis, showed improvement of 6.42 rank points compared to control (covariate corrected model p-value = 0.14). All six efficacy outcomes favored RT001-treated patients compared to controls, demonstrating similar treatment effects across scales ranging from 4.5 to 7.3 rank points. Most notably, the pre-specified exploratory end point of survival demonstrated a mortality risk decrease of 88.8% for INAD patients treated with RT001 (Cox proportional regression model corrected for covariates, hazard ratio = 0.112, p=0.014). The pre-specified secondary endpoint, progression free survival (narrowly defined as pneumonia or death event) improved with reduction of 82.5% in morbidity risk (hazard ratio = 0.175, p=0.021) for patients treated with RT001.

Conclusions There was statistically significant improvement in survival, and trends toward improvement in all functional assessments, in children treated with RT001 compared to the natural history cohort. We posit that these results are clinically meaningful, and suggest that RT001 can slow disease progression in children with INAD.

Authors/Disclosures
Alexander J. Fay, MD, PhD (UCSF Dept. of Neurology) PRESENTER	Dr. Fay has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Retrotope. Dr. Fay has received personal compensation in the range of $0-$499 for serving as a Consultant for Teladoc. Dr. Fay has received personal compensation in the range of $0-$499 for serving as a Consultant for Guidepoint. Dr. Fay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeglea. Dr. Fay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . Dr. Fay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Curry Rockefeller Group. Dr. Fay has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aspiro. Dr. Fay has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Dwyer Hernandez. Dr. Fay has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Gallagher Bassett. Dr. Fay has received research support from Sarepta. The institution of Dr. Fay has received research support from Preston-Werner Ventures.
	No disclosure on file
	No disclosure on file
Frederic Heerinckx, PharmD (Retrotope, Inc.)	No disclosure on file
Mark Midei, MD (Retrotope)	Dr. Midei has received personal compensation for serving as an employee of Retrotope. Dr. Midei has received stock or an ownership interest from Retrotope.
	No disclosure on file