Skip to main content
eScholarship
Open Access Publications from the University of California

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

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

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203712/pdf/nihms610949.pdf
No data is associated with this publication.
Abstract

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.Sebelipase alfa (1mg/kg or 3mg/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.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.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).

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item