Regulatory Decision Summary for Accel-sevelamer
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
Sevelamer carbonate is a polymeric amine that binds phosphate salts from food present in the gastro-intestinal (GI) tract, and thus prevents phosphates from being absorbed into the bloodstream. Thus, in patients with chronic renal failure, prescribing sevelamer is a therapeutic option to lower their characteristically high serum phosphate levels.
Sevelamer carbonate is available on the Canadian market as 800 mg immediate release tablets under the name Renvela, and marketed by Sanofi-Aventis Canada Inc. In this submission, to seek market authorization, the sponsor endeavors to demonstrate that Accel-Sevelamer is bioequivalent to the Renvela product of the originator.
In conventional bioequivalence studies, the bioavailability of a formulation is compared to an approved formulation that contains the same active ingredient to support the claim of similar efficacy and safety. As sevelamer is non-absorbable, bioavailability studies were not an option. The sponsor presented instead the results of 2 in-vitro equivalence studies comparing the sponsors sevelamer carbonate 800 mg tablets with Renvela 800 mg tablets. These studies follow a United States Food and Drug Administration (FDA) design as described in the "Draft Guidance on Sevelamer Carbonate". In addition to the in-vitro studies, the results of a pharmacodynamic clinical study were submitted, comparing the safety and efficacy of the sponsors sevelamer carbonate to that of Renvela in end-stage renal disease patients undergoing dialysis: the intended target population.
Why was the decision issued?
The purpose of this New Drug Submission (NDS) was to seek approval of Accel-Sevelamer carbonate 800 mg formulation. To support the approval, the sponsor provided evidence to support the equivalence of Accel-Sevelamer to the approved Canadian reference product, Renvela, marketed in Canada by Sanofi-Aventis Canada, Inc.
The sponsor submitted results from three studies: 2 in-vitro studies and one randomised, double-blind clinical study in patients with end-stage renal disease on dialysis.
An in-vitro, modified bioavailability study showed that the binding capacity of Accel-Sevelamer is well within standard bioequivalence margins relative to the reference product Renvela. Another pharmacokinetic in-vitro study showed that the time course and extent of the phosphate binding of Accel-Sevelamer was comparable to Renvela.
A 16-week, randomized, double-blind, multiple dose crossover study in 90 chronic kidney disease patients on hemodialysis was submitted to compare the safety and equivalence of serum phosphate control by the Accel-Sevelamer carbonate 800 mg tablet formulation with that of Renvela 800 mg tablets. Treatment with the two formulations showed comparable numbers of adverse events (AEs). None of the AEs were judged as probably or definitely related to study medication. One patient in each group was withdrawn from the study due to an AE. The AEs were not formulation- or dose-related. Comparison of the 2 treatments showed equivalence between the two products regarding their ability to control serum phosphate levels.
Based on the demonstrated equivalence of Accel-Sevelamer carbonate 800 mg tablets, in terms of safety and efficacy, to Renvela, a Notice of Compliance (NOC) was issued.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| ACCEL-SEVELAMER | 02461501 | ACCEL PHARMA INC | SEVELAMER CARBONATE 800 MG |