Long-term safety and efficacy of velmanase alfa treatment in children under 6 years of age with alpha-mannosidosis: A phase 2, open label, multicenter study

TY - JOUR

T1 - Long-term safety and efficacy of velmanase alfa treatment in children under 6 years of age with alpha-mannosidosis: A phase 2, open label, multicenter study

AU - Guffon, Nathalie

AU - Konstantopoulou, Vassiliki

AU - Hennermann, Julia B

AU - Muschol, Nicole

AU - Bruno, Irene

AU - Tummolo, Albina

AU - Ceravolo, Ferdinando

AU - Zardi, Giulia

AU - Ballabeni, Andrea

AU - Lund, Allan

N1 - © 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.

PY - 2023/7

Y1 - 2023/7

N2 - Alpha-mannosidosis (AM) is a rare, autosomal recessive, lysosomal storage disorder caused by alpha-mannosidase deficiency that leads to the accumulation of mannose-rich oligosaccharides. AM symptoms and severity vary among individuals; consequently, AM is often not diagnosed until late childhood. Velmanase alfa (VA), a recombinant human lysosomal alpha-mannosidase product, is the first enzyme replacement therapy indicated to treat non-neurological symptoms of AM in Europe. Previous studies suggested that early VA treatment in children may produce greater clinical benefit over the disease course than starting treatment in adolescents or adults; however, long-term studies in children are limited, and very few studies include children under 6 years of age. The present phase 2, multicenter, open-label study evaluated the safety and efficacy of long-term VA treatment in children under 6 years of age with AM. Five children (three males) received VA weekly for ≥24 months, and all children completed the study. Four children experienced adverse drug reactions (16 events) and two experienced infusion-related reactions (12 events). Most (99.5%) adverse events were mild or moderate, and none caused study discontinuation. Four children developed antidrug antibodies (three were neutralizing). After VA treatment, all children improved in one or more efficacy assessments of serum oligosaccharide concentrations (decreases), hearing, immunological profile, and quality of life, suggesting a beneficial effect of early treatment. Although the small study size limits conclusions, these results suggest that long-term VA treatment has an acceptable safety profile, is well tolerated, and may provide potential benefits to patients with AM under 6 years of age.

AB - Alpha-mannosidosis (AM) is a rare, autosomal recessive, lysosomal storage disorder caused by alpha-mannosidase deficiency that leads to the accumulation of mannose-rich oligosaccharides. AM symptoms and severity vary among individuals; consequently, AM is often not diagnosed until late childhood. Velmanase alfa (VA), a recombinant human lysosomal alpha-mannosidase product, is the first enzyme replacement therapy indicated to treat non-neurological symptoms of AM in Europe. Previous studies suggested that early VA treatment in children may produce greater clinical benefit over the disease course than starting treatment in adolescents or adults; however, long-term studies in children are limited, and very few studies include children under 6 years of age. The present phase 2, multicenter, open-label study evaluated the safety and efficacy of long-term VA treatment in children under 6 years of age with AM. Five children (three males) received VA weekly for ≥24 months, and all children completed the study. Four children experienced adverse drug reactions (16 events) and two experienced infusion-related reactions (12 events). Most (99.5%) adverse events were mild or moderate, and none caused study discontinuation. Four children developed antidrug antibodies (three were neutralizing). After VA treatment, all children improved in one or more efficacy assessments of serum oligosaccharide concentrations (decreases), hearing, immunological profile, and quality of life, suggesting a beneficial effect of early treatment. Although the small study size limits conclusions, these results suggest that long-term VA treatment has an acceptable safety profile, is well tolerated, and may provide potential benefits to patients with AM under 6 years of age.

KW - Male

KW - Adult

KW - Adolescent

KW - Humans

KW - Child

KW - Child, Preschool

KW - alpha-Mannosidosis

KW - Quality of Life

KW - alpha-Mannosidase/adverse effects

KW - Lysosomes

KW - Antibodies

U2 - 10.1002/jimd.12602

DO - 10.1002/jimd.12602

M3 - SCORING: Journal article

C2 - 36849760

VL - 46

SP - 705

EP - 719

JO - J INHERIT METAB DIS

JF - J INHERIT METAB DIS

SN - 0141-8955

IS - 4

ER -