Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results

Abstract

Background Olipudase alfa is a recombinant human acid sphingomyelinase (ASM) enzyme replacement therapy (ERT) for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). We report 2-year cumulative safety and efficacy data after olipudase alfa treatment in 20 children (four adolescents [12–17 year], nine children [6–11 year], and seven infants/early child [1–5 year]) with baseline splenomegaly and growth deficits who completed the 1-year ASCEND-Peds clinical trial (NCT02292654) and who continue to receive olipudase alfa in a long-term study (NCT02004704). Efficacy endpoints include spleen and liver volumes, diffusing capacity of the lung for carbon monoxide (DLCO), high-resolution computed tomography (HRCT) lung imaging, lipid profiles, liver function tests, and height Z-scores. Results All 20 former ASCEND-Peds patients completed at least 2 years of olipudase alfa treatment. No patient discontinued and no new safety issue arose during the second year of treatment; 99% of adverse events were mild or moderate. During year 2, one patient had two treatment-related serious events of hypersensitivity that resolved. Mean reductions from baseline in spleen and liver volumes were 61% and 49%, respectively (p < 0.0001) and mean percent-predicted-DLCO increased by 46.6% (p < 0.0001) in nine patients who performed the test at baseline. Lipid profiles and elevated liver transaminase levels that improved or normalized by 1 year remained stable. Mean height Z-scores improved in all age groups (mean change from baseline 1.17, P < 0.0001). Conclusion Olipudase alfa was generally well-tolerated during 2 years of treatment. Improvements in clinically relevant disease endpoints observed during the first year of treatment were maintained or augmented in the second year. Trial registration NCT02004704 registered 26 Nov 2013, https://clinicaltrials.gov/ct2/show/record/NCT02004704.

Enzyme replacement therapy for children with acid sphingomyelinase deficiency in the real world: A single center experience in Taiwan

“…One-year results indicate good tolerability of the drug and clinically meaningful improvements. Two-year results showing continuing benefits from the first to second years for children has been reported as well [ 27 ]. However, no data outside of clinical trials have been reported yet.…”

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

“…The improvements in clinical disease measures were consistent with those reported in other olipudase alfa trials in adults and children with chronic ASMD [ 8 , 9 , 11 – 13 ]. Adults receiving 2 years of olipudase alfa treatment had continued improvement and, in some cases, normalization of clinical manifestations over time, which has also been demonstrated in the pediatric population after 2 years of treatment [ 12 ] and for five adults receiving olipudase alfa for 6.5 years [ 13 ]. Overall, individuals had improvements in clinical measures of ASMD irrespective of baseline severity, as shown by individual responses, and improvements persisted or continued in the second year of treatment.…”

Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann–Pick disease types A, B and A/B)

“…Importantly, hypersensitivity reactions including anaphylaxis occurred in some paediatric patients. In summary, olipudase alfa was well-tolerated in children and adults and, after treatment (1 year in adult and 2 years in children), resulted in improved lung function, reductions in spleen and liver volumes, improved platelet counts and lipid profiles, reductions in disease biomarkers, and improved growth (in children) [ 85 , 86 , 127 – 129 ].…”