First Doses Given in Clinical Trial of Antisense Oligonucleotide for C9orf72-Associated Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Multiple participants have had initial doses of an antisense oligonucleotide (ASO) (WVE-004; Wave Life Sciences, Cambridge, MA) being evaluated for treatment of C9orf72-associated amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). 

This ASO is designed to block translation of messenger RNA (mRNA) that includes the hexanucleotide repeat expansions associated with C9-ALS and C9-FTD. In the FOCUS-C9 trial (NCT04931862), approximately 50 participants will be randomly assigned to receive 1 of 4 doses of the ASO or placebo via intrathecal infusion.

“The predicted pharmacology of WVE-004, afforded by PN chemistry and based upon in vivo models, allowed us to design FOCUS-C9 to be adaptive, enabling data-driven decisions regarding dose level and frequency as the trial proceeds and potentially accelerating time to proof-of-concept,” said Michael Panzara, MD, MPH, chief medical officer and head of therapeutics discovery and development, Wave Life Sciences. “Opening the FOCUS-C9 trial to those diagnosed with C9orf72-associated ALS or FTD may also facilitate the ability to pursue both indications in the future.” 

Additional objectives include measurement of polyGP DPR proteins in the cerebrospinal fluid (CSF), plasma and CSF pharmacokinetics, and exploratory biomarkers and clinical outcomes.