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 Supplemental New Drug Submission (SNDS) was submitted to propose the use of dapagliflozin (medicinal ingredient in Forxiga) in combination with a dipeptidyl peptidase 4 (DPP-4) inhibitor (alone or with metformin), when the existing therapy, with diet and exercise, does not provide adequate glycemic control.
Why was the decision issued?
Safety and efficacy data from a single pivotal Phase III trial (D1690C00010) were provided in support of the proposed indication. The primary efficacy endpoint was the placebo adjusted reduction in glycated hemoglobin A1c (HbA1c) from baseline to week 24 of treatment, and persistence of efficacy was assessed at the 48-week time point.
Dapagliflozin 10 mg daily improved glycemic control when added to sitagliptin treatment with and without metformin, with a placebo-adjusted reduction in mean HbA1c of 0.48% after 24 weeks of treatment in the overall group, of 0.56% in the dapagliflozin with sitagliptin stratum, and of 0.40% in the dapagliflozin with sitagliptin plus metformin stratum. Improved glycemic control was supported by secondary endpoints of reduction in mean fasting plasma glucose and mean HbA1c in patients with baseline HbA1c ≥8%. The reductions in HbA1c observed after 24 weeks were remained acceptable at week 48.
Since the single trial was conducted with sitagliptin, there was uncertainty as to the efficacy and safety on the use of dapagliflozin as add-on to all DPP-4 inhibitors, as proposed by the sponsor. Since the agents in this class have not been shown to be identical, the added indication was revised and limited to the add-on to sitagliptin with or without metformin.
Dapagliflozin as add-on therapy to sitagliptin alone or in combination with metformin was well tolerated and no new safety concerns were identified. Higher incidences of hypovolemia, genital infection, urinary tract infections and renal impairment were expected based on the known safety profile of dapagliflozin. Risk mitigation is addressed through adequate labelling and the existing risk management plan.
The benefits of the indication studied outweigh the potential risks.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.