Enzymes Approved for Therapy

Abstract

Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of disorders, some rare. The introduction and regulatory approval of 24 different purified enzymes, most of them recombinant preparations, has enabled, often for the first time, effective enzyme therapies. These therapies include enzyme-replacement therapies for some lysosomal storage disorders including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases, lysosomal acid lipase deficiency (sebelipase alfa), and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, tenecteplase, and streptokinase); hypophosphatasia (asfotase alfa); cystic fibrosis (dornase alfa); chronic gout (pegloticase); tumor lysis syndrome (rasburicase); leukemia (L-asparaginase); some collagen-based disorders such as Dupuytren’s contracture (collagenase); severe combined immunodeficiency disease (pegademase bovine); detoxification of methotrexate (glucarpidase); vitreomacular adhesion (ocriplasmin) and as a spreading agent, in particular for drugs (hyaluronidase). The development of these efficacious and safe enzyme-based therapies has gone hand-in-hand with remarkable advances in preparation of the often specifically designed recombinant enzymes; the manufacturing expertize necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.