Alnylam's Nucresiran Shows Sustained TTR Reduction in Phase 1 ATTR Amyloidosis Trial

Key Insights

• Alnylam's nucresiran, a next-generation RNAi therapy, demonstrated rapid and substantial TTR knockdown in healthy subjects in a Phase 1 trial.
• Single doses of 300 mg or higher achieved mean TTR reductions greater than 90% from baseline at Day 15, sustained through at least Day 180.
• Peak TTR level reductions exceeded 96% by Day 29 at these doses, with levels remaining reduced by over 70% at Day 360 after a single 300 mg dose.

New data from Alnylam Pharmaceuticals' Phase 1 study of nucresiran (ALN-TTRsc04), an investigational RNAi therapeutic for transthyretin (ATTR) amyloidosis, were presented at the American Heart Association Scientific Sessions 2024 in Chicago, showcasing promising results for this next-generation treatment. The study evaluated the safety, pharmacodynamics, and pharmacokinetics of single doses of nucresiran in healthy volunteers.

Robust TTR Knockdown

The results indicated that a single dose of nucresiran at 300 mg or higher induced rapid and significant reduction of serum TTR, with minimal variability among patients. Specifically, mean TTR reductions exceeded 90% from baseline by Day 15 and were sustained for at least 180 days. The maximum reduction in mean TTR levels surpassed 96% by Day 29 at these doses.

Sustained Effects

Notably, serum TTR levels remained substantially reduced at Day 360, demonstrating a mean reduction of over 70% following a single 300 mg dose. Data for the 600 mg and 900 mg dose cohorts at Day 360 are still pending. To date, all doses of nucresiran have been well tolerated by study participants.

The ongoing Phase 1 trial is designed as a dose-finding study to assess the safety profile, pharmacodynamics, and pharmacokinetic properties of single ascending doses of nucresiran in healthy subjects. These early results suggest the potential for nucresiran to provide a significant and sustained reduction in TTR levels, a key factor in managing ATTR amyloidosis.