Regulatory Decision Summary for Kivexa
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 Supplement to a New Drug Submission (SNDS) was to expand the indication and dosing regimen to include the treatment of pediatric patients weighing at least 25 kg, in combination with other antiretroviral agents for the treatment of Human Immunodeficiency Virus (HIV) infection. The purpose of this SNDS was also to update the product safety information.
Why was the decision issued?
Health Canada considers that the benefits of the changes in the indication and dosing regimen for Kivexa (abacavir and lamivudine) in the Human Immunodeficiency Virus Type 1 (HIV-1)-infected pediatric population (weighing at least 25 kg) outweighs the potential risks.
Benefits
The clinical efficacy of Kivexa was evaluated in an open-label, parallel group, randomized controlled study (the ARROW trial) which assessed the safety and efficacy of once-daily versus (vs.) twice-daily dosing in pediatric patients aged 3 months to 17 years. The patients were dosed in accordance with the World Health Organization (WHO) recommendations.
Overall, 669 patients aged 3 months to 17 years were randomized into the once daily vs. twice daily treatment groups of the ARROW study. At Week 48, the proportions of patients with a concentration of plasma HIV-1 ribonucleic acid (RNA) less than 80 copies/mL for twice daily dosing was 242/333 (73%), compared to 236/336 (72%) for once daily dosing. The difference was -1.6% [95% confidence interval (CI): -8.4% to 5.2%]. At Week 96, the proportions of patients with a concentration of plasma HIV-1 RNA less than 80 copies/mL for twice daily dosing was 234/333 (72%), compared to 230/336 (69%) for once daily dosing. The difference was -2.3% (95% CI: -9.3% to 4.7%). Once daily dosing of Kivexa was demonstrated to be non-inferior to twice daily dosing in terms of virologic suppression at both Week 48 and 96 as differences in viral load between the two treatment groups were well within the pre-specified 12% non-inferiority margin.
Risks
Kivexa was generally well tolerated during the clinical study program. No additional safety issues were identified in 669 HIV-1-infected pediatric patients receiving either once- or twice-daily dosing compared to adults. There was no difference between the once daily vs. twice daily groups for all Grade 3/4 adverse events or serious adverse events, WHO Stage 3/4 HIV events, weight-for-age, or height-for-age. One Grade 3/4 adverse event in the once daily treatment group (hepatitis Grade 4) was judged as being uncertainly related to abacavir and lamivudine and none of the serious adverse events were considered related to abacavir or lamivudine. There were no adverse events directly leading to treatment modification. There were no abacavir-related hypersensitivity reactions reported during the once daily vs. twice daily randomized group of the ARROW study. All safety concerns have been included in the Kivexa Product Monograph.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.