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Open Access 01-12-2023 | Research

Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial

Authors: Melissa P. Wasserstein, Robin Lachmann, Carla Hollak, Antonio Barbato, Renata C. Gallagher, Roberto Giugliani, Norberto Bernardo Guelbert, Julia B. Hennermann, Takayuki Ikezoe, Olivier Lidove, Paulina Mabe, Eugen Mengel, Maurizio Scarpa, Ebubekir Senates, Michel Tchan, Jesus Villarrubia, Beth L. Thurberg, Abhimanyu Yarramaneni, Nicole M. Armstrong, Yong Kim, Monica Kumar

Published in: Orphanet Journal of Rare Diseases | Issue 1/2023

Abstract

Background

Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DL_CO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment.

Results

Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DL_CO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DL_CO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event.

Conclusion

Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy.

Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691

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Title: Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial
Authors: Melissa P. Wasserstein
Robin Lachmann
Carla Hollak
Antonio Barbato
Renata C. Gallagher
Roberto Giugliani
Norberto Bernardo Guelbert
Julia B. Hennermann
Takayuki Ikezoe
Olivier Lidove
Paulina Mabe
Eugen Mengel
Maurizio Scarpa
Ebubekir Senates
Michel Tchan
Jesus Villarrubia
Beth L. Thurberg
Abhimanyu Yarramaneni
Nicole M. Armstrong
Yong Kim
Monica Kumar
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2023
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-023-02983-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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