Regulatory Decision Summary for Elfabrio

The purpose of this New Drug Submission (NDS) for a New Active Substance (NAS) is to seek market authorization for Elfabrio (pegunigalsidase alfa for injection). Elfabrio is a lysosomal glycosphingolipid-specific enzyme proposed for the treatment of adults with confirmed Fabry disease (alpha-galactosidase A deficiency).

The clinical benefit of Elfabrio in adults with Fabry disease (FD) is supported by findings from a Phase 1/2 and a pivotal Phase 3 study. Elfabrio demonstrated a sustained, substantial reduction in globotriaosylceramide (Gb3) accumulation within renal peritubular capillaries (PTCs) and slowed glomerular filtration rate (eGFR) decline. The renal effects were comparable to an approved enzyme replacement therapy (ERT; agalsidase beta), which has the same mechanism of action.

The safety assessment was based primarily on the pivotal Phase 3 study, supplemented by 7 additional clinical studies. The safety database indicates that Elfabrio has an acceptable safety profile, consistent with agalsidase beta. The primary safety concerns were severe hypersensitivity, including anaphylaxis, and infusion-associated reactions (IARs).

Numerically higher cardiac, cerebrovascular, renal, and non-cardiac death events were reported in the Elfabrio group, but interpretation is limited by the small number of events, prior ERT exposure, and disease progression. Additional uncertainty remains in treatment-naïve patients: while few were enrolled, available data suggest a potentially higher rate of related IARs or hypersensitivity reactions compared with ERT-experienced subjects.

The identified risks are reflected in the Product Monograph and will be monitored post-market through routine pharmacovigilance activities, as outlined in the Risk Management Plan.

Overall, the benefit-risk profile was considered favourable for Elfabrio (pegunigalsidase alfa for injection, 1 mg/kg) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance was recommended.

The Risk Management Plan (RMP) for Elfabrio (pegunigalsidase alfa) was submitted to Health Canada as part of a New Drug Submission (NDS; Control number 287986). The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP is considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures for Elfabrio. This included providing information in the product monograph, the availability of additional testing for patients and the development of training materials for healthcare professionals. The RMP also identified areas where more data are needed. Results related to safety of Elfabrio from ongoing and planned studies will be submitted in Periodic Safety Update Reports (PSURs)/Periodic Benefit Risk Evaluation Reports (PBRERs) as they become available.

The chemistry and manufacturing information submitted for Elfabrio has demonstrated that the drug substance and drug product have been well characterized and can be consistently manufactured to meet the approved specifications.

The labelling material submitted met all applicable regulations and guidance.

For further details about Elfabrio (pegunigal sidase alfa), please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.