TY - JOUR
T1 - Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD)
T2 - sustained improvements in clinical outcomes after 6.5 years of treatment in adults
AU - Lachmann, Robin H.
AU - Diaz, George A.
AU - Wasserstein, Melissa P.
AU - Armstrong, Nicole M.
AU - Yarramaneni, Abhimanyu
AU - Kim, Yong
AU - Kumar, Monica
N1 - Funding Information:
The authors thank the study patients and the staff of the Mount Sinai clinical research facility (US) and the Charles Dent Metabolic Unit at the National Hospital for Neurology and Neurosurgery (UK). Patrice C Ferriola, Ph.D. of KZE PharmAssociates provided medical writing assistance and was funded by Sanofi. Lisa Underhill of Sanofi provided editorial review.
Funding Information:
The authors thank the study patients and the staff of the Mount Sinai clinical research facility (US) and the Charles Dent Metabolic Unit at the National Hospital for Neurology and Neurosurgery (UK). Patrice C Ferriola, Ph.D. of KZE PharmAssociates provided medical writing assistance and was funded by Sanofi. Lisa Underhill of Sanofi provided editorial review.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Background: Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD. Results: After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment. Conclusions: Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1.
AB - Background: Enzyme replacement therapy with olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is indicated for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children and adults. An ongoing, open-label, long-term study (NCT02004704) assessed the safety and efficacy of olipudase alfa in 5 adults with ASMD. Results: After 6.5 years of treatment, there were no discontinuations, no olipudase-alfa-related serious adverse events, and no new safety signals compared to earlier assessments. Most treatment-emergent adverse events were mild in intensity (1742/1766, 98.6%). Among treatment-related adverse events (n = 657), more than half were considered infusion-associated reactions (n = 403, 61.3%) such as headache, nausea, abdominal pain, arthralgia, pyrexia, and fatigue. No patient developed neutralizing anti-drug antibodies to cellular uptake, and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Improvements (decreases) in spleen and liver volumes progressed through 6.5 years (mean changes from baseline of -59.5% and -43.7%, respectively). There was a mean increase in diffusing capacity of the lung for carbon monoxide from baseline of 55.3%, accompanied by improvements in interstitial lung disease parameters. Lipid profiles at baseline indicated dyslipidemia. All patients had sustained decreases in pro-atherogenic lipid levels and increases in anti-atherogenic lipid levels following olipudase alfa treatment. Conclusions: Olipudase alfa is the first disease-specific treatment for ASMD. This study demonstrates that long-term treatment with olipudase alfa is well-tolerated and is associated with sustained improvements in relevant disease clinical measures. NCT02004704 registered 26 November 2013, https://clinicaltrials.gov/ct2/show/NCT02004704?term=NCT02004704&draw=2&rank=1.
KW - Acid sphingomyelinase deficiency
KW - Niemann-Pick disease type B and type A/B
KW - Olipudase alfa
KW - Recombinant human acid sphingomyelinase
UR - http://www.scopus.com/inward/record.url?scp=85153826542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85153826542&partnerID=8YFLogxK
U2 - 10.1186/s13023-023-02700-x
DO - 10.1186/s13023-023-02700-x
M3 - Article
C2 - 37098529
AN - SCOPUS:85153826542
SN - 1750-1172
VL - 18
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 94
ER -
