Alnylam Pharmaceuticals has announced positive interim data from its Phase I trial of nucresiran, an RNAi therapeutic being developed for the treatment of transthyretin (ATTR) amyloidosis. The study demonstrated significant and sustained reductions in serum TTR levels following a single dose, suggesting the potential for less frequent dosing in future treatments.
Significant TTR Reduction
The Phase I trial evaluated the safety, pharmacokinetics, and pharmacodynamics of nucresiran in healthy individuals. Results showed that a single 300mg dose led to a mean serum TTR reduction of over 90% by day 15, which was maintained through day 180. By day 360, the TTR reduction remained substantial, at over 70%. Data for higher doses (600mg and 900mg) are still pending.
The trial also reported low inter-patient variability in TTR reduction. In the 300mg cohort, TTR reduction ranged from 96% to 96.7% by day 29. The 600mg cohort saw reductions between 96.6% and 98.6%, while the 900mg cohort experienced reductions between 96% and 97.3%.
Tolerability and IKARIA Platform
The study highlighted that nucresiran was well-tolerated, with most adverse events classified as mild and unrelated to the treatment. Nucresiran is developed using Alnylam's IKARIA platform, which aims to provide deeper and more durable TTR knockdown, potentially allowing for less frequent dosing.
Future Development
While the safety and efficacy of nucresiran are yet to be established by regulatory bodies such as the FDA and EMA, Alnylam anticipates initiating Phase III development plans for nucresiran in Q1 2025.
Expert Commentary
Alnylam Pharmaceuticals' chief medical officer, Pushkal Garg, stated, "We are very excited by these new Phase I data with nucresiran, our next-generation TTR-targeting RNAi therapeutic, which demonstrated that a single dose of ≥300mg achieved rapid knockdown of TTR greater than 90% from day 15 that was sustained to at least six months. Furthermore, we are encouraged by the potential of nucresiran to reduce interpatient variability in TTR lowering...representing a potential new paradigm in the treatment of ATTR amyloidosis."
About ATTR Amyloidosis
ATTR amyloidosis is a life-threatening condition characterized by the accumulation of misfolded TTR proteins as amyloid deposits, affecting multiple organs and tissues throughout the body.
