BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

Vestronidase alfa, an enzyme replacement therapy, is an approved drug for the treatment of MPS VII. The approval of this drug has set a precedent for future drug development for the regulators and drug developers. First, the pivotal clinical trial was conducted to evaluate the totality of the clinical data for determining the efficacy of the treatment, therefore, no primary clinical endpoint was established. Second, the drug obtains approval positive outcome on the secondary endpoint; changes in the urinary glycosaminoglycan, from placebo control. The glycosaminoglycan is also the pharmacodynamic biomarker that reflected the efficacy of the drug. Third, the novel multi-domain clinical responder index was designed to evaluate the treatment outcomes and included six minutes walk test (6MWT), forced vital capacity (FVC), shoulder range motion, visual acuity, BOT-2 fine, and gross motor activity. While MRDI evaluation per subject suggested the stabilization of clinical condition if no...

Immune response associated adverse events and hypersensitivity reactions are the major safety concerns related to enzyme replacement therapies. The immunogenicity against these therapeutic enzymes depends on structural similarities, manufacturing processes, formulation, and impurities etc. The drug developer has developed strategies to mitigate manufacturing related immunogenicity risk with improved processes such as optimization of the protein sequence, mammalian cell lines to express and purify recombinant human enzymes. Despite these efforts, the immunogenicity and anti-drug antibody generation against these therapeutic proteins are heterogeneous among the populations. In the same dose cohort, one subject may produce higher anti-drug antibodies titer with lesser efficacy. In contrast, another subject may have less or no anti-drug antibodies with no impact on drug efficacy. Identify and characterizing these individual factors would enable a better understanding of individual fact...