A Systematic Review on Safety and Efficacy of Migalastat for the treatment of Fabry’s Disease

ABSTRACT

Introduction

Fabry’s disease (FD) is a genetic lysosomal storage disorder characterized by α-galactosidase A (α-Gal A) lost/reduced activity. We aim to systematically assess the safety and efficacy of Migalastat, an oral pharmacological chaperone, that has been approved for the treatment of FD in patients with amenable mutations.

Methods

We conducted literature search following the PRISMA guidelines in major databases up to 4 February 2024, for studies that assessed the clinical outcomes of migalastat in patients with FD. The New Castle Ottawa Scale was used to evaluate the quality of the included studies.

Results

A total of 2141 records were identified through database searches and register searches, amongst which 26 records were screened, and 12 of these were excluded. The remaining 14 reports were sought for retrieval. The 12 retrieved articles were assessed for eligibility and their quality was assessed after their inclusion. Amongst the included studies, 5 were of high quality, 6 were of medium quality, and 1 was of low quality.

Conclusion

Migalastat showed varied effects on enzyme activity and substrate levels, with gender-specific differences noted in GL-3 substrate activity and eGFR. Overall, it improved cardiac and renal outcomes similarly to enzyme replacement therapy, with a comparable safety profile.

KEYWORDS:

• Migalastat
• Fabry’s disease
• α-galactosidase A
• lysosomal storage disorder
• efficacy
• pharmacological chaperone

Article highlights

• What is already known on this topic: Before this study, the scientific knowledge about Migalastat’s effectiveness in Fabry disease (FD) was limited but growing. Migalastat, a potential treatment for FD patients with amenable mutations, showed promise in reducing GL-3 levels and improving kidney function, but the evidence was scattered.

• What this study adds: This systematic review consolidated the existing literature and provided valuable insights into Migalastat’s impact on FD.

• How this study might affect research, practice, or policy: The analysis found that Migalastat effectively reduced GL-3 levels, potentially benefiting kidney function and quality of life. It also emphasized the need for further long-term research to understand the safety and durability of Migalastat treatment.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2024.2354466

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Ethical statement

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Author contributions

Conception and design were done by H Majid and Nidhi; Analysis and interpretation of the data were done H Majid, N Verma, S Bhandari, and S Gupta; the drafting of the paper was done by H Majid, N Verma, S Bhandari, and S Gupta; revising it critically for intellectual content was done by Nidhi and H Majid; and the final approval of the version to be published was carried out by H Majid, N Verma, S Bhandari, S Gupta, and Nidhi and all authors agree to be accountable for all aspects of the work.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a consultant and are on the Amicus board of advisers as well as speaker bureau. These activities are paid. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Data availability statement

All data for this systematic review have been included within the manuscript.

Additional information

Funding

This paper was not funded.