Enzyme replacement therapy in patients who have mucopolysaccharidosis i and are younger than 5 years: Results of a multinational study of recombinant human α-L-iduronidase (laronidase)

OBJECTIVE. Our objective was to evaluate the safety, pharmacokinetics, and efficacy of laronidase in young, severely affected children with mucopolysaccharidosis I. METHODS. This was a prospective, open-label, multinational study of 20 patients who had mucopolysaccharidosis I and were <5 years old (16 with Hurler syndrome, 4 with Hurler-Scheie syndrome) and were scheduled to receive intravenous laronidase at 100 U/kg (0.58 mg/kg) weekly for 52 weeks. Four patients underwent dosage increases to 200 U/kg for the last 26 weeks because of elevated urinary glycosaminoglycan levels at week 22. RESULTS. Laronidase was well tolerated at both dosages. Investigators reported improved clinical status in 94% of patients at week 52. The mean urinary glycosaminoglycan level declined by ∼50% at week 13 and was sustained thereafter. A more robust decrease in urinary glycosaminoglycan was observed in patients with low antibody levels and those who were receiving the 200 U/kg dosage. On examination, the liver edge was reduced by 69.5% in patients with a palpable liver at baseline and week 52 (n = 10). The proportion of patients with left ventricular hypertrophy decreased from 53% to 17%. Global assessment of sleep studies showed improvement or stabilization in 67% of patients, and the apnea/hypopnea index decreased by 5.8 events per hour (-8.5%) in those with abnormal baseline values. The younger patients with Hurler syndrome (<2.5 years) and all 4 patients with Hurler-Scheie syndrome showed normal mental development trajectories during the 1-year treatment period. CONCLUSIONS. Laronidase seems to be well tolerated and to provide clinical benefit in patients who have severe mucopolysaccharidosis I and are <5 years old. Enzyme replacement therapy is not curative and may not improve all affected organs and systems in individuals when irreversible changes have developed. The long-term clinical outcome and effects of antibodies and laronidase dosing on glycosaminoglycan reduction warrant additional investigation.