Abstract | PURPOSE: METHODS: A phase 2/3, 52 week, international, double-blind, placebo-controlled trial (ASCEND; NCT02004691/EudraCT 2015-000371-26) enrolled 36 adults with ASMD randomized 1:1 to receive olipudase alfa or placebo intravenously every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary efficacy endpoints were percent change from baseline to week 52 in percent predicted diffusing capacity of the lung for carbon monoxide and spleen volume (combined with splenomegaly-related score in the United States). Other outcomes included liver volume/function/ sphingomyelin content, pulmonary imaging/function, platelet levels, lipid profiles, and pharmacodynamics. RESULTS: Least square mean percent change from baseline to week 52 favored olipudase alfa over placebo for percent predicted diffusing capacity of the lung for carbon monoxide (22% vs 3.0% increases, P = .0004), spleen volume (39% decrease vs 0.5% increase, P < .0001), and liver volume (28% vs 1.5% decreases, P < .0001). Splenomegaly-related score decreased in both groups (P = .64). Other clinical outcomes improved in the olipudase alfa group compared with the placebo group. There were no treatment-related serious adverse events or adverse event-related discontinuations. Most adverse events were mild. CONCLUSION:
Olipudase alfa was well tolerated and associated with significant and comprehensive improvements in disease pathology and clinically relevant endpoints compared with placebo in adults with ASMD.
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Authors | Melissa Wasserstein, Robin Lachmann, Carla Hollak, Laila Arash-Kaps, Antonio Barbato, Renata C Gallagher, Roberto Giugliani, Norberto Bernardo Guelbert, Takayuki Ikezoe, Olivier Lidove, Paulina Mabe, Eugen Mengel, Maurizio Scarpa, Eubekir Senates, Michel Tchan, Jesus Villarrubia, Yixin Chen, Sandy Furey, Beth L Thurberg, Atef Zaher, Monica Kumar |
Journal | Genetics in medicine : official journal of the American College of Medical Genetics
(Genet Med)
Vol. 24
Issue 7
Pg. 1425-1436
(07 2022)
ISSN: 1530-0366 [Electronic] United States |
PMID | 35471153
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
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Copyright | Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Recombinant Proteins
- Carbon Monoxide
- Sphingomyelin Phosphodiesterase
- olipudase alfa
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Topics |
- Adult
- Carbon Monoxide
(therapeutic use)
- Double-Blind Method
- Enzyme Replacement Therapy
(methods)
- Humans
- Niemann-Pick Disease, Type A
- Recombinant Proteins
- Sphingomyelin Phosphodiesterase
- Splenomegaly
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