Background and Aims: Lysosomal acid lipase deficiency is characterized by hepatomegaly and dyslipidaemia, which can lead to cirrhosis and premature atherosclerosis. Sebelipase alfa is an approved recombinant human lysosomal acid lipase. In an open-label extension study of adults with lysosomal acid lipase deficiency (LAL-CL04), sebelipase alfa treatment for 1 year reduced serum transaminase levels and liver fat content and improved serum lipid levels. Methods: Final data from LAL-CL04 are reported herein for patients who received sebelipase alfa infusions (1.0 or 3.0 mg/kg every other week) for up to 5 years. Results: Of 8 patients enrolled, 7 received sebelipase alfa for 224-260 weeks; 1 was lost to follow-up. Median baseline levels of alanine aminotransferase and aspartate aminotransferase (81.5 and 50.0 U/L, respectively) were decreased through the end-of-study visit (54.0 and 34.0 U/L). Median low-density lipoprotein cholesterol decreased from 113 to 78 mg/dL, total cholesterol decreased from 171 to 132 mg/dL, and high-density lipoprotein cholesterol increased from 37 to 42 mg/dL. Most treatment-emergent adverse events were nonserious (99%), mild/moderate (98%) and unrelated to sebelipase alfa (87%); no patient discontinued as a result of treatment-emergent adverse events. One patient had 2 serious treatment-emergent adverse events (cholecystitis and cholelithiasis; assessed as unlikely related to sebelipase alfa). Two patients had 20 nonserious infusion-associated reactions in weeks 6-38; all were manageable. One patient tested positive for antidrug antibodies (single occurrence). Conclusions: Sebelipase alfa was well tolerated and improved serum transaminase and lipid levels for up to 5 years in adults with lysosomal acid lipase deficiency. Trial registration number: ClinicalTrials.gov record NCT01488097.
Bibliographical noteFunding Information:
Editorial and medical writing support was provided by Jessica D. Herr, PharmD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ and was funded by Alexion Pharmaceuticals, Inc, the study sponsor. In collaboration with the study sites, the sponsor designed and conducted the study, collected the data, monitored conduct of the study and performed the statistical analyses. The interpretation of the data was performed by the sponsor in collaboration with all of the authors. Alexion Pharmaceuticals, Inc provided review of this manuscript for the authors' consideration.
VM received funding for participation as a study investigator and an honorarium for chairing an educational session from Alexion Pharmaceuticals, Inc JBA and RS have received honoraria for educational sessions and funding from Alexion Pharmaceuticals, Inc for participation as study investigators. JK has given lectures on this topic supported by Alexion Pharmaceuticals, Inc, and has received funding from Alexion Pharmaceuticals, Inc for participation as a study investigator. MB is a member of the LALD scientific registry and has received honoraria for participation in advisory boards and funding from Alexion Pharmaceuticals, Inc for participation as a study investigator. CBW received consultancy fees and funding from Alexion Pharmaceuticals, Inc for providing education on lysosomal diseases. SM and FA are employees of and may own stock/options in Alexion Pharmaceuticals, Inc
- enzyme replacement therapy
- lysosomal storage diseases
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't