• Open Access

Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients With cholesteryl ester storage disease


  • Potential conflict of interest: Synageva Biopharma Corp. is the manufacturer of sebelipase alfa and conducted the statistical analysis. All authors had access to the study data, reviewed early and final drafts of the article, and are fully responsible for the content and editorial decisions related to the article. Drs. Burg, Quinn, and Schneider own stocks in and are employees of Synageva BioPharma. Dr. Deegan received grants from Synageva BioPharma. Dr. Eckert is an employee of Synageva BioPharma. Dr. Jones consults for and advises Synageva BioPharma. Dr. Wraith received grants from Synageva BioPharma, Genozyme, BioMarin, and Shire.

  • See Editorial on Page 850

  • Supported by Synageva BioPharma Corp. and in part by grant UL1TR000067 from the National Center for Advancing Translational Sciences, National Institutes of Health to the Mount Sinai School of Medicine and by research project PRVOUK-P24/LF1/3 to TH.

Address reprint requests to: Anthony G. Quinn, MBChB, PhD, FRCP, Synageva BioPharma Corp., 128 Spring St., Suite 520, Lexington, MA 02421. E-mail:


Cholesteryl ester storage disease (CESD), an inherited deficiency of lysosomal acid lipase (LAL), is an underappreciated cause of progressive liver disease with no approved therapy. Presenting features include dyslipidemia, elevated transaminases, and hepatomegaly. To assess the clinical effects and safety of the recombinant human LAL, sebelipase alfa, nine patients received four once-weekly infusions (0.35, 1, or 3 mg·kg−1) in LAL-CL01, which is the first human study of this investigational agent. Patients completing LAL-CL01 were eligible to enroll in the extension study (LAL-CL04) in which they again received four once-weekly infusions of sebelipase alfa (0.35, 1, or 3 mg·kg−1) before transitioning to long-term every-other-week infusions (1 or 3 mg·kg−1). Sebelipase alfa was well tolerated, with mostly mild adverse events unrelated to sebelipase alfa. No antidrug antibodies were detected. Transaminases decreased in patients in LAL-CL01 and increased between studies. In seven patients receiving ongoing sebelipase alfa treatment in LAL-CL04, the mean ± standard deviation (SD) decreases for alanine transaminase and aspartate aminotransferase at week 12 compared to the baseline values in LAL-CL01 were 46 ± 21 U/L (−52%) and 21 ± 14 U/L (−36%), respectively (P ≤ 0.05). Through week 12 of LAL-CL04, these seven patients also showed mean decreases from baseline in total cholesterol of 44 ± 41 mg/dL (−22%; P = 0.047), low density lipoprotein-cholesterol of 29 ± 31 mg/dL (−27%; P = 0.078), and triglycerides of 50 ± 38 mg/dL (−28%, P = 0.016) and increases in high density lipoprotein-cholesterol of 5 mg/dL (15%; P = 0.016). Conclusion: These data establish that sebelipase alfa, an investigational enzyme replacement, in patients with CESD is well tolerated, rapidly decreases serum transaminases, and that these improvements are sustained with long-term dosing and are accompanied by improvements in serum lipid profile. (HEPATOLOGY 2013;58:950–957)