Wave Life Sciences’ WVE-006 Delivers 64% M-AAT, 71% Z-AAT Reduction
Wave Life Sciences’ WVE-006 achieved a mean 64% wild-type M-AAT and 71% reduction in mutant Z-AAT with 200 mg biweekly dosing, and sustained 13.6 µM total AAT with 400 mg monthly treatment in Phase 1b/2a RestorAATion-2. The drug maintained editing effects for at least three months and targets FDA accelerated approval by mid-2026.
1. RestorAATion-2 Trial Results
Data from the 200 mg biweekly and 400 mg monthly cohorts showed WVE-006 generated wild-type M-AAT comprising 64% and 58.7% of total AAT respectively, reduced Z-AAT by 71% (200 mg biweekly) and 67.7% (400 mg monthly), with total AAT levels of 11.9 µM and 13.6 µM.
2. Dynamic Acute Phase Responses
Three participants exhibited acute phase responses with C-reactive protein elevation correlating with rapid AAT increases, including one reaching 20.6 µM post-single 200 mg dose and two achieving 57.8% and 59.8% M-AAT rises during mild infections.
3. Safety Profile and RNA Editing Advantages
WVE-006 was generally safe and well tolerated with no liver toxicities reported; GalNAc-RNA editing avoids permanent genome alterations and off-target edits associated with DNA editing or lipid nanoparticle delivery.
4. Regulatory Timeline and Next Steps
Wave Life Sciences plans FDA feedback on an accelerated approval pathway by mid-2026 and will host an investor webcast to discuss the Phase 1b/2a data and development strategy.