Comparison of elapegademase and pegademase in ADA‐deficient patients and mice. (9th February 2020)

• Record Type: Journal Article
• Authors: Murguia‐Favela, L.; Min, W.; Loves, R.; Leon‐Ponte, M.; Grunebaum, E.
• Is Part Of: Clinical and experimental immunology. Volume 200:Number 2(2020)
• Page Start: 176
• Page End: 184
• Publication Date: 2020-02-09
• Subjects: adenosine deaminase deficiency -- elapegademase -- enzyme replacement therapy -- pegademase -- severe combined immunodeficiency; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.13420
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: The absence of adenosine deaminase (ADA) causes severe combined immune deficiency (SCID), which has been treated with PEGylated bovine‐extracted ADA (ADAGEN). ADAGEN was recently replaced by a PEGylated recombinant bovine ADA, expressed in Escherichia coli (elapegademase, ELA–ADA). Limited information on ELA–ADA is available. ADA enzymatic activity of ELA–ADA and ADAGEN was assessed in vitro at diverse dilutions. ADA activity and immune reconstitution in an ADA–SCID patient treated with ELA–ADA were compared with age‐matched patients previously treated with ADAGEN. ADA activity and thymus reconstitution were evaluated in ADA‐deficient mice following ELA–ADA or ADAGEN administered from 7 days postpartum. In vitro, ADA activity of ELA–ADA and ADAGEN were similar at all dilutions. In an ADA–SCID patient, ELA–ADA treatment led to a marked increase in trough plasma ADA activity, which was 20% higher than in a patient previously treated with ADAGEN. A marked increase in T cell numbers and generation of naive T cells was evident following 3 months of ELA–ADA treatment, while T cell numbers increased following 4 months in 3 patients previously treated with ADAGEN. T cell proliferations stimulation normalized and thymus shadow became evident following ELA–ADA treatment. ADA activity was significantly increased in the blood of ADA‐deficient mice following ELA–ADA compared to ADAGEN, while both treatments improved the mice weights, the weight, number of cells in their thymus and thymocyte subpopulations. ELA–ADA has similar in‐ vitro and possibly better in‐vivo activity than ADAGEN. Future studies will determine whether ELA–ADA results in improved long‐term immune reconstitution. Abstract : 1. Elapegademase, a PEGylated recombinant form of bovine adenosine deaminase, has similar in vitro and possibly better in vivo activity than PEGylated bovine adenosine deaminase, ADAGEN.2. Elapegademase treatment led to a marked increase of T cell numbers and generation of naïve T cells within 3 months in an ADA‐deficient patient with severe combined immune deficiency.