ALN-6457

ALN-6457 is an experimental, intrathecally administered small interfering RNA (siRNA) therapeutic designed to treat prion diseases, including Creutzfeldt-Jakob disease (CJD). Developed by Regeneron Pharmaceuticals in collaboration with Alnylam Pharmaceuticals, ALN-6457 utilizes Alnylam's proprietary C16 lipid conjugation technology to facilitate delivery and sustained distribution within the central nervous system (CNS). The drug works via RNA interference (RNAi) to target and silence the *PRNP* mRNA, which encodes the major prion protein (PrP). By reducing the production of normal cellular prion protein, ALN-6457 aims to deplete the substrate required for the propagation of toxic, misfolded prions, thereby slowing or halting neurodegeneration. In September 2026, ALN-6457 was authorized for exceptional compassionate use in Brazil, and it is being evaluated in a Phase 1/2 clinical trial for symptomatic prion disease.