Regulatory Decision Summary for Soliris

The purpose of this submission for Soliris (eculizumab for injection) is to seek the pediatric indication for the treatment of paroxysmal nocturnal hemoglobinuria.

The pediatric indication for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) has been authorized for Soliris, with dose regimens for patients weighing 5 kg to less than 40 kg. The dose regimens by body weight are based on a weight-based pharmacokinetic (PK) model in adult patients with PNH. This same PK model was previously used for dosing regimens in pediatric patients with atypical hemolytic uremic syndrome. Thus, the same posology is proposed in pediatrics for both indications.

An open label study in 7 pediatric patients aged 11 to 17 years evaluated the adequacy of the proposed dose regimens (pharmacokinetic and pharmacodynamic parameters) as a primary objective; and the safety, tolerability, and efficacy of eculizumab as secondary objectives. The eculizumab serum concentrations predicted by the population PK model were within the therapeutic target range of 50 to 700 µg/mL of eculizumab during both the induction and maintenance phases of treatment in these patients weighing between 48.6 to 69.8 kg. Eculizumab treatment in adolescents with PNH resulted in a full inhibition of hemolytic activity, and no patient displayed hemolysis breakthrough. The adequacy of the dosing regimen in patients with a body weight lower than 40 kg was previously confirmed in pediatrics with atypical hemolytic uremic syndrome.

Soliris was well tolerated in adolescents with PNH. Common adverse events included abdominal pain, fatigue, headache, hypotension, pain in extremity and fever. The safety profile in adolescents appears similar to the one in adults with PNH. An important risk with the use of Soliris is its mode of action in blocking the terminal complement activation; therefore patients have an increased risk of infections especially with Neisseria and encapsulated bacteria. In this study, all infections (i.e. acute sinusitis, catheter site cellulitis, otitis media acute and upper respiratory tract infection) were mild to moderate in severity and judged unrelated to treatment with eculizumab.

Overall, the benefit-harm-uncertainty profile was favourable for Soliris for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Soliris, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.