Safety and efficacy of laronidase in Chinese patients with mucopolysaccharidosis type I: a phase IV, single-arm, open-label, multicenter study

Abstract

Background: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by deficiency of the enzyme α-L-iduronidase. Laronidase (Aldurazyme^®) stands as the sole FDA-approved enzyme replacement therapy (ERT) for MPS I to date. In June 2020, a concentrated solution of laronidase for injection received approval for a Chinese bioproduct license, exempted from clinical trials. Compliance with approval requirements mandates post-marketing surveillance (PMS) for laronidase. The objective of this study was to evaluate the safety and efficacy of laronidase treatment at a dosage of 100 U/kg body weight weekly in Chinese patients with MPS I.

Methods: From October 2021 to July 2023, 12 MPS I patients at four institutions in China received weekly intravenous injections of laronidase at a dose of 100 U/kg of body weight once a week for 26 weeks. The primary efficacy endpoint was the percentage change in urinary glycosaminoglycans (uGAGs) levels at week 26 relative to baseline. Safety endpoints included the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs, including infusion-related reactions) during the treatment period (TE).

Results: Laronidase consistently reduced uGAGs levels from baseline to week 26, with a percentage change of -64.61% ± 26.90% (95% CI: -81.70% to -47.52%). There was a revealed reduction following laronidase treatment. The percentage reductions in uGAGs from baseline to weeks 2, 4, 8, 12, and 20 were decreased. The decreases in absolute change of uGAGs were observed at weeks 2, 4, 8, 12, 20, and 26. The percentage reduction in liver volume from baseline to week 26 was - 13.24% ± 7.86% (95% CI: -18.24% to -8.25%). Nine participants (75%) achieved an overall treatment compliance rate ≥80%. Eleven participants (91.7%) experienced treatment-emergent adverse events (TEAEs). Four participants (33.3%) experienced AESIs.

Conclusions: In Chinese patients with MPS I, laronidase as an enzyme replacement therapy effectively reduces glycosaminoglycan storage and liver volume while demonstrating a favorable safety profile.

Clinical trial registration number: NCT05134571.

Clinical trial registration date: 2021-10-21.

Name of the registry: China Post-marketing Surveillance (PMS) Study of Aldurazyme^®. URL OF THE TRIAL REGISTRY RECORD: https://clinicaltrials.gov/search?term=NCT05134571.

Keywords: Chinese; Enzyme replacement therapy; Laronidase; Mucopolysaccharidosis type I; Phase IV study.