No clinical benefit seen in trial of novel treatment for ALS, frontotemporal dementia

Key takeaways:

• No significant changes were reported in CSF protein or white blood cell count with WVE-004 vs. placebo, although treatment was generally safe and well-tolerated.
• Wave Life Sciences optedResRe to discontinue production.

Topline results from a phase 1b/2a study evaluating an investigational therapy for C9orf72-associated ALS and frontotemporal dementia revealed no clinical benefit after 24 weeks of treatment compared with placebo.

According to a press release from Wave Life Sciences, the antisense oligonucleotide WVE-004, which selectively targets transcriptional variants containing hexanucleotide repeat expansion (G₄C₂) associated with the C9orf72 gene, was compared with placebo at multiple 10 mg doses every 12 or 4 weeks and also as a 20 mg single dose. The investigational treatment was generally safe and well-tolerated across doses, with mostly mild adverse events.

However, the company reported no clinically meaningful changes in cerebrospinal fluid protein or white blood cell count since the previous update in April 2022, and although there were reductions in the biomarker poly(GP) from baseline, they were not associated with improved functional outcomes. Based on these findings, the company has opted to discontinue development of WVE-004.

“While we again saw substantial reductions of poly(GP) with multiple doses, we are deeply disappointed that we were not able to see any evidence of potential benefits that would be expected to drive meaningful outcomes for these patients,” Paul Bolno, MD, MBA, president and CEO of Wave Life Sciences, said in the release. “C9-ALS/FTD is complex and made all the more challenging by the absence of a clinically validated biomarker.”