Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial

Journal of Inherited Metabolic Disease
Line BorgwardtAllan M Lund

Abstract

This phase III, double-blind, randomised, placebo-controlled trial (and extension phase) was designed to assess the efficacy and safety of velmanase alfa (VA) in alpha-mannosidosis (AM) patients. Twenty-five patients were randomised to weekly 1 mg/kg VA or placebo for 52 weeks. At study conclusion, placebo patients switched to VA; 23 patients continued receiving VA in compassionate-use/follow-on studies and were evaluated in the extension phase [last observation (LO)]. Co-primary endpoints were changes in serum oligosaccharide (S-oligo) and in the 3-min stair-climb test (3MSCT). Mean relative change in S-oligo in the VA arm was -77.6% [95% confidence interval (CI) -81.6 to -72.8] at week 52 and -62.9% (95% CI -85.8 to -40.0) at LO; mean relative change in the placebo arm was -24.1% (95% CI -40.3 to -3.6) at week 52 and -55.7% (95% CI -76.4 to -34.9) at LO after switch to active treatment. Mean relative change in 3MSCT at week 52 was -1.1% (95% CI -9.0 to 7.6) and - % (95% CI -13.4 to 6.5) for VA and placebo, respectively. At LO, the mean relative change was 3.9% (95% CI -5.5 to 13.2) in the VA arm and 9.0% (95% CI -10.3 to 28.3) in placebo patients after switch to active treatment. Similar improvement pattern was observed in se...Continue Reading

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Jun 7, 2015·Orphanet Journal of Rare Diseases·Line BorgwardtAllan Meldgaard Lund

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Citations

Jun 27, 2019·American Journal of Medical Genetics. Part a·Daphné LehalleLaurence Faivre
Feb 26, 2020·Cells·Miroslava DidiášováRitva Tikkanen
May 1, 2020·Frontiers in Molecular Biosciences·Jacob M FavretDaesung Shin
Oct 1, 2020·Orphanet Journal of Rare Diseases·Julia B HennermannNicole M Muschol
Nov 20, 2019·JIMD Reports·Sara S CatheyLucia Horowitz
Nov 25, 2020·Advances in Therapy·Elena VerrecchiaRaffaele Manna
Dec 12, 2020·Frontiers in Molecular Biosciences·Mariola J Edelmann, Gustavo H B Maegawa
Dec 16, 2020·Molecular Genetics and Metabolism·Jitka MajovskaPetr Dusek

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