Two-year results of the ASCEND trial of olipudase alfa adults with chronic acid sphingomyelinase deficiency show parallel improvements in former placebo patients and further improvement in continuing olipudase alfa patients
Molecular Genetics and Metabolism
; 135(2):S126-S127, 2022.
Article
in English
| EMBASE | ID: covidwho-1677224
ABSTRACT
Acid sphingomyelinase deficiency (ASMD) is a rare debilitating lysosomal disease characterized by pulmonary dysfunction, hepatosplenomegaly, and dyslipidemia. Olipudase alfa, intravenous-recombinant-human ASM, is in late-stage development (Sanofi Genzyme) for non-central-nervous-system manifestations of ASMD. We report 2-year outcomes for 33/36 ASMD adults with splenomegaly (mean baseline spleen volume 11.3 multiples of normal [MN]) and respiratory impairment (mean baseline percent-predicted-diffusing capacity for carbon monoxide [DLCO] 49.3%) who participated in the 1-year double-blind placebo-controlled primary-analysis period [PAP] of the ASCEND trial of olipudase alfa (NCT02004691) and completed a second year in the open-label extension. Patients underwent gradual dose-escalation to 3.0 mg/kg/2-weeks. During the PAP, olipudase-alfa-treated compared to placebo-treated patients (11 randomization) had statistically significant increases in DLCO and decreases in spleen and liver volume. One placebo patient withdrew during year-1. In year-2, improvements in former placebo patients paralleled the olipudase-alfa group in the PAP (all values ANCOVA LS-mean percent change from trial baseline ± SEM) DLCO increased 28.0 ± 6.2% (n = 10);spleen volume decreased 36.0 ± 3.0% (n = 11);liver volume decreased 30.7 ± 2.5% (n = 11). Olipudase-alfa patients who received 2 years of treatment continued improving DLCO increased 28.5 ± 6.2%, n = 10 (year-1 increase 22.2 ± 3.4%, n = 17);spleen volume decreased 47.0 ± 2.7%, n = 14 (year-1 decrease 39.5 ± 2.4%, n = 17), liver volume decreased 33.4 ± 2.2%, n = 14 (year-1 decrease 27.8 ± 2.5, n = 17). Improvements in dyslipidemia, liver function, liver sphingomyelin clearance, and plasma lyso-sphingomyelin in former placebo patients paralleled those seen in olipudase-alfa patients in the PAP;continuing olipudase-alfa patients maintained these benefits in year-2. Overall, 99% of treatment-emergent adverse events were mild/moderate, with one treatment-related serious adverse event. During year-2, six patients missed ≥1 assessments and one patient discontinued due to COVID-19 travel restrictions;one additional patient discontinued (withdrawal of consent). In summary, during year-2 of ASCEND, crossover-placebo patients improved to a similar extent as olipudase-alfa patients in year-1 and patients continuing on olipudase alfa showed sustained or further improvements.
olipudase alfa; placebo; sphingomyelin; sphingosylphosphorylcholine; adult; analysis of covariance; clinical article; clinical trial; conference abstract; controlled study; coronavirus disease 2019; diffusing capacity for carbon monoxide; double blind procedure; drug therapy; drug withdrawal; dyslipidemia; female; human; human tissue; liver function; liver weight; male; Niemann Pick disease; randomization; randomized controlled trial; spleen size; splenomegaly; travel restriction
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Type of study:
Randomized controlled trials
Language:
English
Journal:
Molecular Genetics and Metabolism
Year:
2022
Document Type:
Article
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