Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency

Vassili Valayannopoulos, Vera Malinova, Tomas Honzík, Manisha Balwani, Catherine Breen, Patrick B. Deegan, Gregory M. Enns, Simon A. Jones, John P. Kane, Eveline O. Stock, Radhika Tripuraneni, Stephen Eckert, Eugene Schneider, Gavin Hamilton, Michael S. Middleton, Claude Sirlin, Bruce Kessler, Christopher Bourdon, Simeon A. Boyadjiev, Reena SharmaChris Twelves, Chester B. Whitley, Anthony G. Quinn

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Background & Aims: Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Methods: Sebelipase alfa (1 mg/kg or 3 mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. Results: 216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of 58% and 40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were 60%, 39%, 36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Conclusions: Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184).

Original languageEnglish (US)
Pages (from-to)1135-1142
Number of pages8
JournalJournal of Hepatology
Issue number5
StatePublished - 2014
Externally publishedYes


  • Dyslipidemia
  • Enzyme replacement
  • Fatty liver
  • Hepatomegaly
  • Lysosomal storage

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)


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