A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency

Barbara K. Burton, Manisha Balwani, Francois Feillet, Ivo Baric, T. Andrew Burrow, Carmen Camarena Grande, Mahmut Coker, Alejandra Consuelo-Sanchez, Patrick Deegan, Maja Di Rocco, Gregory M. Enns, Richard Erbe, Fatih Ezgu, Can Ficicioglu, Katryn N. Furuya, John Kane, Christina M Laukaitis, Eugen Mengel, Edward G. Neilan, Scott NightingaleHeidi Peters, Maurizio Scarpa, K. Otfried Schwab, Vratislav Smolka, Vassili Valayannopoulos, Marnie Wood, Zachary Goodman, Yijun Yang, Stephen Eckert, Sandra Rojas-Caro, Anthony G. Quinn

Research output: Contribution to journalArticle

121 Scopus citations


BACKGROUND Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia. METHODS In this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile. RESULTS Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol (=190 mg per deciliter) in 38 of 66 patients (58%) and cirrhosis in 10 of 32 patients (31%) who underwent biopsy. A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment. At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P = 0.03), with mean changes from baseline of -58 U per liter versus -7 U per liter (P

Original languageEnglish (US)
Pages (from-to)1010-1020
Number of pages11
JournalNew England Journal of Medicine
Issue number11
StatePublished - Sep 10 2015


ASJC Scopus subject areas

  • Medicine(all)

Cite this

Burton, B. K., Balwani, M., Feillet, F., Baric, I., Burrow, T. A., Grande, C. C., Coker, M., Consuelo-Sanchez, A., Deegan, P., Di Rocco, M., Enns, G. M., Erbe, R., Ezgu, F., Ficicioglu, C., Furuya, K. N., Kane, J., Laukaitis, C. M., Mengel, E., Neilan, E. G., ... Quinn, A. G. (2015). A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. New England Journal of Medicine, 373(11), 1010-1020. https://doi.org/10.1056/NEJMoa1501365