A recent report (BK Burton et al. NEJM 2015; 373: 1010-20, editorial 1071-1) provides preliminary evidence of efficacy of Sebeliplase Alfa for lysosomal acid lipase deficiency.
In this multicenter, randomized, double-blind, placebo-controlled study of 66 patients, enzyme replacement therapy with Sebelipase alfa was examined (1 mg intravenously every other week). After 20 weeks, all patients were treated by open-label. Of the 32 patients who had had liver biopsies, 10 (31%) were noted to have cirrhosis.
- Alanine aminotransferase normalized in 11 (36%) of treated patients compared with 2 (7%) of controls
- Improvement in lipid levels and reduction in hepatic fat content were evident in treated patients (P<0.001 for all comparisons, except P-0.04 for triglycerides
The editorial provides a schematic explaining how sebelipase alfa targets the hepatocyte (Figure 1). The authors note that “longer-term follow-up in a larger number of patients will be required for confirmation.”
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