Regulatory Decision Summary for Ixiaro
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.
Product type:
Drug
Medicinal ingredient(s):
Japanese Encephalitis Vaccine, (inactivated, adsorbed)
Therapeutic area:
Active immunizing agent
Type of submission:
Supplement to a New Drug Submission
Control number:
203520
What was the purpose of this submission?
The purpose of this Supplement to a New Drug Submission (SNDS) is to extend the indication and dosage recommendation of Ixiaro with the addition of a paediatric indication (2 months of age and older), a rapid immunization schedule for adults (18-65 years of age), a recommendation for a second booster dose for adults (18-65 years of age) and additional data for Ixiaro in the elderly (≥65 years of age).
Why was the decision issued?
- The Use of Ixiario Primary and Booster Dose in Paediatric Population (2 Months to Less Than 18 Years of Age):
The clinical data from four pediatric studies demonstrated that Ixiaro produced a strong immune response against the Japanese Encephalitis virus (JEV) in the pediatric population (>2 months to <18 years). The long-term protection rate was enhanced by a booster dose (at Month 12) as evidenced by a significant immune response and sustained 100% protection rates for 2 years after the booster, which support the recommendation of a booster dose at Month 12 for children who will travel to or live in the endemic area. Data analysis also indicated that in the same age-group (≥ 3 years to < 12 years), the higher dose (0.5 mL) induced higher immune response than the lower dose (0.25 mL). The doses proposed for licensure are 0.25 mL in children aged 2 months to <3 years and 0.5 mL in children aged 3 years and above. The safety data indicated that Ixiaro at doses of 0.25mL or 0.5 mL was well tolerated in children from 2 months to <18 years from both endemic and non- endemic areas. The safety profile was comparable with adult data. A booster dose was well tolerated with adverse event (AE) rates lower compared to the primary series, the majority of AEs being of mild intensity. There are no significant long-term safety concerns with Ixiaro identified from these studies.
Overall the safety and immunogenicity data from the four phase III studies support Ixiaro vaccination in children aged >2 month to <18 years. In addition, the Japanese Encephalitis (JE) is a potentially debilitating and fatal disease for which there is no drug treatment available. Therefore the proposed change to include pediatric population (>2 months to <18 years) to the indication of Ixiaro is considered to be acceptable. - Additional Rapid Immunization Schedule For Adults (18-65 Years Of Age)
Clinical trials showed that immunization with Ixiaro co-administered with Rabipur (rabies vaccine) in a rapid schedule (at Day 0, 7) is comparable to both immunizations with Ixiaro alone in the conventional schedule (Day 0, 28) and immunization with Ixiaro concomitantly with Rabipur in the conventional schedules. The rapid schedule resulted in virtually identical immune response of 99% (rapid schedule) vs. 100% (in both conventional schedule groups). The kinetic of antibody response showed similar decline rate for accelerated and conventional regimen.
The safety results indicated that the accelerated schedule had similar risk/benefit profile with that to the conventional schedule for the JE vaccine. There were no significant safety concerns identified in this study. - Long-Term Antibody Persistence And Second Booster Recommendation For Adults (18-65 Years Of Age)
A mathematical model showed that the average protection is estimated to last for a total of 14 years after the booster dose (range 2 to 25 years), and 75% of vaccinees are projected to remain protected for 10 years after the first booster dose.
Based on the long-term immunogenicity data and the applied mathematical modeling, the proposed change of adding a second booster dose at 10 years after the first booster to the Product Monograph is considered to be acceptable.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.