Idursulfase Beta (Hunterase, DB16190): A Comprehensive Review of Its Pharmacology, Clinical Development, and Regulatory Landscape for Hunter Syndrome

1. Introduction to Idursulfase Beta (Hunterase)

1.1. Overview and Therapeutic Indication: Hunter Syndrome (Mucopolysaccharidosis Type II)

Idursulfase beta is a biotechnologically derived enzyme replacement therapy (ERT) developed for the treatment of Mucopolysaccharidosis Type II (MPS II), commonly known as Hunter syndrome.[1] Hunter syndrome is a rare, X-linked lysosomal storage disorder characterized by a deficiency or absence of the enzyme iduronate-2-sulfatase (IDS).[1] This enzymatic deficiency leads to the progressive, systemic accumulation of glycosaminoglycans (GAGs)—specifically dermatan sulfate and heparan sulfate—within lysosomes of various cells and tissues. This accumulation results in cellular dysfunction and widespread organ damage, contributing to the multisystemic and progressive nature of the disease.[1]

The fundamental pathogenic mechanism of Hunter syndrome, namely the deficiency of IDS and subsequent GAG accumulation, directly informs the rationale for ERT. By providing a functional, exogenous form of the IDS enzyme, ERT aims to restore the catabolism of accumulated GAGs, thereby mitigating or slowing disease progression. The systemic nature of GAG accumulation underscores the challenge of ERT, as the therapeutic enzyme must ideally reach all affected tissues, including those protected by biological barriers such as the blood-brain barrier, to address the full spectrum of clinical manifestations.