ENOrphanet Journal of Rare Diseases | Long Ruilin et al. Safety and efficacy of Laronidase in Chinese MPS I patients: A phase IV single-arm open-label multicenter study
Date: April 05, 2025
Classification: Frontiers
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This study provides the first assessment of Laronidase's safety and efficacy in Chinese MPS I patients, demonstrating significant reductions in urinary glycosaminoglycans and liver volume with good tolerability.
Literature Overview
This article titled 'Safety and efficacy of laronidase in Chinese patients with mucopolysaccharidosis type I: a phase IV, single-arm, open-label, multicenter study' published in the Orphanet Journal of Rare Diseases reviews the efficacy and safety of Laronidase in Chinese MPS I patients. The study enrolled 12 MPS I patients who received weekly 100 U/kg Laronidase treatment for 26 weeks, showing average reductions of 64.61% in urinary glycosaminoglycans (uGAGs) and 13.24% in liver volume with good treatment compliance. Safety assessments revealed 91.7% of patients experienced treatment-emergent adverse events (TEAEs), mostly mild to moderate, while 33.3% reported adverse events of special interest (AESIs) - all infusion-associated reactions (IARs). The article summarizes global research background of Laronidase for MPS I treatment, highlights its proven efficacy and safety as enzyme replacement therapy (ERT) in multiple clinical studies, and emphasizes the importance of population-specific adaptation in Chinese patients and future research directions. No new safety signals were identified, providing initial evidence for Laronidase application in Chinese MPS I patients.
Background Knowledge
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by IDUA gene mutations leading to reduced or absent IDUA enzyme activity. This causes glycosaminoglycans (GAGs) accumulation in tissues, resulting in multi-system damage. The disease spectrum includes severe (Hurler syndrome), intermediate (Hurler-Scheie), and mild (Scheie syndrome) phenotypes, with global incidence rates of 0.69-1.66/100,000. Current primary treatments include hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT), with Laronidase (Aldurazyme®) being the FDA-approved ERT for non-neurological MPS I symptoms. HSCT is primarily indicated for severe cases ≤2.5 years old, while ERT shows efficacy across all phenotypes, particularly in improving hepatosplenomegaly, pulmonary function, and joint mobility. However, ERT treatment costs remain high, and long-term efficacy/safety requires further validation in specific populations. This study fills critical clinical data gaps for Laronidase in Chinese MPS I patients, providing foundation for treatment optimization.
Study Methods and Experimental Design
This phase IV post-marketing surveillance (PMS) study (NCT05134571) employed a multicenter, single-arm, open-label design. Twelve Chinese MPS I patients aged ≥5 years received weekly intravenous Laronidase at 100 U/kg for 26 weeks. The primary efficacy endpoint was percentage change in uGAGs levels at week 26. Secondary endpoints included liver volume changes, dynamic monitoring of uGAGs levels throughout treatment, and safety assessments. All patients were recruited from four Chinese medical centers with average treatment exposure of 27.19 weeks, analyzed using modified intent-to-treat (mITT) population.
Key Findings and Perspectives
Research Implications and Future Directions
This study represents the first evaluation of Laronidase's efficacy and safety in Chinese populations, with results supporting its effectiveness in reducing uGAGs and liver volume consistent with global clinical trials. However, due to limited sample size and short follow-up period, future studies should focus on long-term efficacy and impacts on other clinical endpoints (e.g., pulmonary function, joint mobility, vision). Additionally, anti-drug antibody (ADA) testing was not conducted, which should be incorporated in future studies to assess immunogenicity. This research provides foundation for subsequent larger-scale and longer-duration clinical trials in Chinese populations, particularly across Asian countries.
Conclusion
This study marks the first assessment of Laronidase's efficacy and safety (100 U/kg weekly) in Chinese MPS I patients, demonstrating significant reductions in uGAGs levels and liver volume with good tolerability. 91.7% of patients experienced adverse events, predominantly mild to moderate, with no new safety signals identified. 75% of patients achieved treatment compliance ≥80%, indicating Laronidase's clinical application potential in Chinese MPS I patients. However, due to limited sample size and 26-week follow-up period, larger cohorts and extended observation are needed to evaluate multidimensional outcomes including cognition, pulmonary function, and vision. The absence of anti-drug antibody (ADA) testing limits immunogenicity assessment. Overall, Laronidase's efficacy in Chinese MPS I populations aligns with global studies, supporting its feasibility as ERT and providing preliminary evidence for subsequent clinical research and real-world application.
The study also highlights that some Chinese MPS I patients opt for HSCT combined with ERT to improve transplant success rates and reduce postoperative complications, though ERT remains valuable for patients with transplant failure or who are ineligible for HSCT. Future research should explore optimized combination strategies between ERT and HSCT, as well as individualized treatment responses across different age groups and genetic mutation backgrounds. This study provides initial support for Laronidase's clinical application in China and contributes to the global understanding of ethnic diversity in MPS I treatment.
Additionally, the study emphasizes the multi-system involvement characteristic of MPS I and the critical role of early diagnosis and intervention in improving prognosis. While Laronidase effectively treats non-neurological symptoms, its impact on central nervous system lesions remains limited, necessitating combination with HSCT for optimal outcomes in severe cases. These findings provide reference data for Chinese and other Asian clinicians, as well as inform public health policy and patient management strategies.
