FDA approves Miplyffa and Aqneursa: a new era in treatment of Niemann-Pick Disease Type C

Abstract In September 2024, the Food and Drug Administration (FDA) approved two novel therapeutic agents, Miplyffa (arimoclomol) in combination with Miglustat and Aqneursa (levacetylleucine), for Niemann-Pick Disease Type C (NPC), a rare and progressive lysosomal storage disorder with limited treatment options. NPC results from mutations in the NPC1 or NPC2 genes that impair intracellular cholesterol trafficking, leading to debilitating neurological and systemic symptoms. Miplyffa upregulates CLEAR genes and enhances the transcription of heat shock proteins, especially HPS 70 which are essential for proper NPC1 folding, stabilizes lysosomal membrane, enhances sphingolipid-degrading enzyme activity, and prevents cellular death. Aqneursa regulates energy metabolism, enhances mitochondrial and lysosomal function, and provides neuroprotective effects. Clinical trials have demonstrated that both drugs slow disease progression and improve patients’ quality of life. These approvals represent a major advancement in NPC treatment, offering hope to patients and their families and emphasizing the importance of continued research.