Alnylam Pharmaceuticals announced positive interim results from its Phase 1 clinical trial of nucresiran (ALN-TTRsc04), a next-generation RNAi therapeutic being developed for the treatment of transthyretin (ATTR) amyloidosis. The data, presented at the American Heart Association Scientific Sessions 2024, demonstrated rapid and sustained knockdown of transthyretin (TTR) protein levels following a single dose of the investigational drug.
Rapid and Sustained TTR Reduction
The Phase 1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of single ascending doses of nucresiran in healthy volunteers. Key findings from the study include:
- A single dose of nucresiran at 300 mg or higher led to a rapid reduction in serum TTR levels, with mean reductions of greater than 90% from baseline achieved by Day 15.
- This significant TTR reduction was sustained for at least six months (Day 180).
- Peak reductions in mean TTR levels of greater than 96% were observed by Day 29.
- At Day 360, a single 300 mg dose still resulted in a mean TTR reduction of greater than 70%.
According to Alnylam, data for the 600 mg and 900 mg dose cohorts at Day 360 are not yet available.
Encouraging Safety Profile
Nucresiran was generally well-tolerated across all tested doses in the Phase 1 trial. The majority of adverse events reported were mild, and none were considered related to the treatment. Importantly, there were no injection site reactions or liver-related safety signals identified.
Potential for Infrequent Dosing
The sustained TTR reduction observed in the study suggests that nucresiran may have the potential for biannual or even annual subcutaneous dosing. This could represent a significant advantage over existing ATTR amyloidosis therapies that require more frequent administration.
Pushkal Garg, M.D., Chief Medical Officer at Alnylam, stated, "We are very excited by these new Phase 1 data with nucresiran...which demonstrated that a single dose of ≥300 mg achieved rapid knockdown of TTR greater than 90% from Day 15 that was sustained to at least six months."
About Nucresiran and ATTR Amyloidosis
Nucresiran is an investigational RNAi therapeutic designed to target and reduce the production of both mutant and wild-type TTR protein, the underlying cause of ATTR amyloidosis. ATTR amyloidosis is a progressive and often fatal disease caused by the accumulation of misfolded TTR protein in various organs and tissues, including the nerves, heart, and gastrointestinal tract.
Alnylam plans to share Phase 3 development plans for nucresiran in the first quarter of 2025.
