Wave Life Sciences Ltd. announced topline results from the Phase 1b/2a FOCUS-C9 study evaluating WVE-004 as an investigational treatment for C9orf72-associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). The results include data from a planned analysis of the study, where participants received multiple 10 mg doses of WVE-004 or placebo every 12 weeks (Q12W) or every 4 weeks (Q4W), as well as an additional 20 mg single dose cohort. WVE-004 was generally safe and well-tolerated across doses, with most adverse events presenting as mild in intensity.

There were no clinically meaningful changes in cerebrospinal fluid (CSF) protein or white blood cell count and no new safety signals since the previous data update in April 2022. Robust, sustained reductions in poly(GP) from baseline were observed, with a maximal mean reduction of 48% (p<0.0001) in the Q12W dose and 50% (p=0.0001) in the Q4W dose of WVE-004. Poly(GP) is a pharmacodynamic biomarker indicating WVE-004 is lowering C9orf72 hexanucleotide repeat expansion (G4C2) transcripts, which are hypothesized to contribute to pathogenesis in C9-ALS/FTD.

However, no clinical benefit was observed at 24 weeks, and reductions in poly(GP) were not associated with stabilization or improvement in functional outcomes. Based on these data, and in the absence of biomarkers reasonably likely to predict clinical outcomes, Wave has decided to discontinue development of WVE-004. Wave remains on track to share data from its Phase 1b/2a SELECT-HD study in Huntington's disease investigating WVE-003 in the second half of 2023.

The company is also rapidly advancing WVE-N531 for Duchenne muscular dystrophy amenable to exon 53 skipping into the potentially registrational Part B (Phase 2) clinical study, following its best-in-class exon skipping data observed in the Part A proof-of-concept study. Wave is also on track to bring the industry's first RNA editing compound, WVE-006, into a clinical trial in Alpha-1 antitrypsin deficiency in the second half of 2023. In addition, the company continues to advance preclinical research with its modalities that restore or repair endogenous proteins, including additional RNA editing programs, and expects to share an update on its preclinical pipeline highlighting new data in the third quarter of 2023.