Nexviazyme

Pompe disease (also known as glycogen storage disease type II, acid maltase deficiency, and glycogenosis type II) is a rare metabolic muscle disease inherited in an autosomal recessive manner defined by a deficiency of acid α-glucosidase (GAA), which is necessary for the degradation of lysosomal glycogen. GAA cleaves alpha-1,4 and alpha-1,6 linkages in glycogen under the acidic conditions of the lysosome. Pompe disease results in intra-lysosomal accumulation of glycogen in various tissues, particularly cardiac and skeletal muscles, leading to the development of cardiomyopathy, progressive muscle weakness, and impairment of respiratory function. Avalglucosidase alfa is a recombinant human acid α-glucosidase (rhGAA) that provides an exogenous source of GAA. Avalglucosidase alfa is a modification of alglucosidase alfa in which approximately 7 hexamannose structures each containing two terminal mannose-6-phosphate (bis-M6P) moieties are conjugated to oxidised sialic acid residues on alglucosidase alfa. Avalglucosidase alfa has a 15-fold increase in mannose-6-phosphate (M6P) moieties compared with alglucosidase alfa. Increasing the level of bis-M6P on rhGAA provides a mechanism to drive uptake into the diaphragm and other skeletal muscle via the cation-independent M6P receptor, where it can degrade glycogen and ameliorate tissue damage.