Evaluation of 2 patients with alpha-mannosidosis and history of conductive hearing impairment participating in a placebo-controlled, phase 3 program receiving velmanase alfa (human recombinant alpha-mannosidase)

Lund, Allan Meldgaard; Borgwardt, Line; Régal, Luc; Cattaneo, Frederica

doi:10.1016/j.ymgme.2020.12.152

Cited by 1 publication

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“…Patients with AM typically have mixed hearing loss, comprised of conductive and sensorineural impairment, the latter of which is often permanent 23 . A previous case study of a pediatric patient with AM reported that conductive hearing and serum IgG levels improved during VA treatment 24 . Children in the present study were assessed for hearing loss.…”

Section: Discussionmentioning

confidence: 85%

“…23 A previous case study of a pediatric patient with AM reported that conductive hearing and serum IgG levels improved during VA treatment. 24 Children in the present study were assessed for hearing loss. One child (patient 3) had sensorineural hearing loss in both ears at baseline and after VA treatment but demonstrated an improvement of 20 dB nHL in the V wave threshold in the right ear at 12 and 24 months.…”

Section: Efficacy Outcomesmentioning

confidence: 99%

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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

Guffon

Konstantopoulou

Hennermann

et al. 2023

J of Inher Metab Disea

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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.

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Section: Discussionmentioning

confidence: 85%

Section: Efficacy Outcomesmentioning

confidence: 99%