Wave Life Sciences Ltd (NASDAQ:WVE) has reported topline results from its Phase 1b/2a FOCUS-C9 study evaluating WVE-004 as a treatment for C9orf72-associated amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD).
Unfortunately, WVE-004 did not show any clinical benefit when compared to placebo. In addition, it was observed that poly(GP) reductions did not correlate with clinical outcomes. Because of these unsatisfactory conclusions, Wave has decided to discontinue the development of WVE-004.
However, the study did show that there were robust, sustained reductions in poly(GP) from baseline. This led to the observation of 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 that indicates WVE-004 lowers C9orf72 hexanucleotide repeat expansion (G4C2) transcripts. These transcripts are believed to contribute to pathogenesis in C9-ALS/FTD.
Despite the negative outcomes, WVE-004 was generally safe and well-tolerated across doses, with most adverse events presenting as mild in intensity. The study also found 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.
Wave is still planning to share data from its Phase 1b/2a SELECT-HD study on WVE-003 in Huntington’s disease, later this year. The company is also progressing with WVE-N531 for Duchenne muscular dystrophy, which is amenable to exon 53 skipping and is being advanced into the potentially registrational Part B (Phase 2) clinical study.
Price Action: WVE shares are down by 15.10% at $3.15 during the premarket session on the last check Tuesday.
