BK Burton et al. JPGN 2022; 74: 757-764. Open Access: Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency
This was open-label study of enzyme replacement therapy (ERT) in 31 children and adults with lysosomal acid lipase deficiency (LALD). Sebelipase Alfa, a recombinant human lysosomal acid lipase, was FDA approved in 2015 for LALD.
- Liver biopsies showed mostly improved or stable histopathology at 48 and 96 weeks versus baseline. In addition, there was modest improvement in transaminases; median ALT and AST levels changed by −42.0 and −22.0 U/L, respectively.
- Median low-density lipoprotein cholesterol levels decreased by 52.6 mg/dL, and median high-density lipoprotein cholesterol increased by 9.8 mg/dL. Though, 55% of the study population had concomitant lipid-modifying therapy
- Two patients tested positive for nonneutralizing, anti-drug antibodies
In the associated commentary (pgs 726-727), the authors state this study showed that “in contrast to infantile disease, ERT is not universally beneficial in individuals with attenuated disease…[and] it is impossible to predict response to ERT.” Testing for LALD is recommended for infants with hepatomegaly, poor growth, diarrhea or adrenal insufficiency. In older groups, LALD needs to be considered in those with hepatomegaly, steatosis, and dyslipidemia.
My take: There are still many questions regarding ERT’s long-term benefit in individuals with LALD, especially those with mild disease.
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