Journal Article

Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study

Jones, Simon A., Slasor, Peter, Burton, Barbara, Scarpa, Maurizio, Hendriksz, Christian J., Mengel, Eugen, Lounsbury, Debra, Giugliani, Roberto, Hughes, Derralynn, Valayannopoulos, Vassili, Dummer, Wolfgang, Lin, Shuan-Pei, Harmatz, Paul, Fleming, Thomas R.

2014

Overview

Objective To assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA). Methods Patients with Morquio A aged ≥5 years ( N  = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated. Results At week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P  = 0.017) for weekly and 0.5 m (95 % CI −17.8, 18.9; P  = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI −2.1, 4.4; P  = 0.494) for weekly and −0.5 stairs/min (95 % CI −3.7, 2.8; P  = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation. Conclusions Elosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile.

• Publisher: Springer Netherlands,Springer,Blackwell Publishing Ltd
• Subject: Adolescent / Adult / Biochemistry / Biological and medical sciences / Carbohydrates (enzymatic deficiencies). Glycogenosis / Child / Child, Preschool / Chondroitinsulfatases - therapeutic use / Double-Blind Method / Enzyme Replacement Therapy - methods / Errors of metabolism / Female / Human Genetics / Humans / Internal Medicine / Keratan Sulfate - urine / Male / Medical genetics / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Middle Aged / Motor Activity / Mucopolysaccharidosis IV - drug therapy / Original / Original Article / Pediatrics / Rare Diseases - drug therapy / Treatment Outcome / Walking / Young Adult