PracticeUpdate Conference Series_WORLDSymposium 2019

Dr. Skuban’s team also evaluated the effect of long-term migalastat treatment on plasma globotria- sosylceramide levels in ATTRACT and its open-label extension study. They examined globotriasosylcer- amide profiles in patients with migalastat-amenable GLA mutations in the trial. They measured plasma globotriasosylceramide levels at baseline and at various subsequent time points. At baseline, defined as the start of migalastat treatment, median globotria- sosylceramide level was lower in females (5.8 nmoL/L minimum, maximum 0.8, 14.7 [n=26]) than in males (10.5 nmoL/L minimum, maximum 0.8, 59.1 [n=18]). Median globotriasosylceramide levels remained low and stable with long-termmigalastat treatment. Median changes from baseline to month 60 were –2.5 nmoL/L in males (n=4) and 0.4 nmoL/L in females (n=6). Assay-to-assay variability of the globotriasosylcer- amide quantification assay is approximately 20%. This variability which may have contributed to visit- to-visit changes.

Dr. Skuban explained that Fabry disease is associated with a pathological accumulation of substrates, including globotriasosylceramide and globotriaosylsphingosine. Though the clinical relevance of globotriasosyl- ceramide as a biomarker for monitoring treatment effect in Fabry remains uncertain, globotriasosyl- ceramide is used widely as a diagnostic indicator of Fabry disease. Dr. Skuban concluded that the data validated primary trial results, but given the uncertainty in the origin of plasma globotriasosylceramide and differences in the biodistribution and mechanism of action among the current treatment options, plasma globotriasosylceramide should not be interpreted as a stand-alone biomarker. Further research is warranted, and clinical out- comes should be considered when assessing treatment efficacy.

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WORLDSymposium 2019 • PRACTICEUPDATE CONFERENCE SERIES 9