Regulatory Decision Summary for FORXIGA
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?
This supplement to a new drug submission was filed to seek approval for the use of Forxiga in combination with metformin and a sulfonylurea, when existing therapy, with diet and exercise, does not provide adequate glycemic control.
Why was the decision issued?
A single Phase IIIb pivotal study in 219 patients with type 2 diabetes and inadequate glycemic control on metformin, in combination with a sulfonylurea, was provided to support the proposed indication. The primary efficacy endpoint, a statistically significant mean placebo adjusted hemoglobin A1c (HbA1c) (glycated hemoglobin) reduction from baseline to week 24 in patients treated with dapagliflozin (the medicinal ingredient in Forxiga) 10 mg daily added-on to metformin in combination with a sulfonylurea, was met.
The placebo-adjusted mean decrease in HbA1c was −0.69%, an effect which was sustained at week 52. Improved glycemic control was supported by the first four key secondary endpoints of reduction in mean fasting plasma glucose, reduction in total body weight, proportion of patients achieving a therapeutic glycemic response (defined as HbA1c <7.0% over 24 weeks of treatment), and reduction in seated systolic blood pressure from baseline to week 8.
Overall, dapagliflozin as add-on therapy in combination with metformin and a sulfonylurea was well tolerated and no new safety concerns were identified. In the 28-week extension period study, incidence of adverse events was increased but remained balanced in the dapagliflozin 10 mg and the placebo group. Higher incidences of genital infection, urinary tract infections, renal impairment, and hypovolemia were reported but expected based on the known safety profile of dapagliflozin. More patients in the dapagliflozin group (15.6%) than in the placebo group (4.6%) also experienced a minor event of hypoglycemia, an event known with this combination.
Risk mitigation is addressed through adequate labelling and the existing risk management plan.
The benefit-risk assessment for the new indication is positive.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.