Regulatory Decision Summary for Adynovate
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?
The purpose of this Supplemental New Drug Submission (SNDS) was to include the pediatric age group (<12 years) with hemophilia A, a genetic bleeding disorder, in the indication for recombinant factor VIII concentrate, Adynovate.
ADVATE, a recombinant FVIII was modified to form Adynovate by chemical linkage to polyethylene glycol - PEG (MW 20 kDa). This change extends the half-life of the product which may allow reduction in the frequency of infusions needed for prophylaxis.
Adynovate is currently authorized for adolescents and adults with hemophilia A for the following:
- control and prevention of bleeding episodes,
- prophylaxis to prevent or reduce the frequency of bleeds
- perioperative management
Why was the decision issued?
Authorization for the pediatric indication was based upon a prospective, uncontrolled, multicenter study evaluating pharmacokinetics, efficacy, safety, and immunogenicity of Adynovate in previously treated pediatric subjects (less than 12 years) receiving prophylaxis. Subjects received Adynovate 40 - 60 IU/kg twice-weekly for 6 months or 50 exposure days (EDs), whichever was longer. There were 66 evaluable subjects.
Important efficacy endpoints were annualized bleeding rate, number of infusions per bleeding episode and hemostatic efficacy rating at resolution of the bleed. In the pediatric study, efficacy results for prophylaxis are in the same range as for other FVIII products but were achieved with twice-weekly infusions. Efficacy for the treatment of bleeding episodes was demonstrated, but most bleeding episodes were treated with higher weight-adjusted doses than guidelines recommend and resolved with one or two infusions.
The most common adverse reactions (ADRs) reported in at least 1% of patients were headache, diarrhea, nausea and rash. These safety findings were consistent with observations from previous trials in adolescents and adults. Serious adverse events, such as inhibitor development or hypersensitivity, have been reported with Adynovate and are common to all rFVIII products.
For many years, PEG has been used as an added ingredient in other products such as vaccines or clotting factors or chemically linked to proteins. Nonclinical studies of Adynovate were designed to evaluate potential toxicity of PEG accumulation but no evidence of PEG accumulation was found, even with very high doses.
Adynovate has a favourable benefit/risk profile and is recommended for approval for the pediatric population under 12 years of age.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.