TY - JOUR
T1 - A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults
T2 - One-year results
AU - Wasserstein, Melissa
AU - Lachmann, Robin
AU - Hollak, Carla
AU - Arash-Kaps, Laila
AU - Barbato, Antonio
AU - Gallagher, Renata C.
AU - Giugliani, Roberto
AU - Guelbert, Norberto Bernardo
AU - Ikezoe, Takayuki
AU - Lidove, Olivier
AU - Mabe, Paulina
AU - Mengel, Eugen
AU - Scarpa, Maurizio
AU - Senates, Eubekir
AU - Tchan, Michel
AU - Villarrubia, Jesus
AU - Chen, Yixin
AU - Furey, Sandy
AU - Thurberg, Beth L.
AU - Zaher, Atef
AU - Kumar, Monica
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/7
Y1 - 2022/7
N2 - Purpose: This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults. 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.
AB - Purpose: This trial aimed to assess the efficacy and safety of olipudase alfa enzyme replacement therapy for non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adults. 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.
KW - Diffusing capacity of the lung for carbon monoxide
KW - Niemann-Pick type A/B
KW - Niemann-Pick type B
KW - Organomegaly
KW - Recombinant human acid sphingo-myelinase
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UR - http://www.scopus.com/inward/citedby.url?scp=85131212347&partnerID=8YFLogxK
U2 - 10.1016/j.gim.2022.03.021
DO - 10.1016/j.gim.2022.03.021
M3 - Article
C2 - 35471153
AN - SCOPUS:85131212347
SN - 1098-3600
VL - 24
SP - 1425
EP - 1436
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 7
ER -