Regulatory Decision Summary for JARDIANCE
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 SNDS sought revisions to the "Indications And Clinical Use" section of the Product Monograph to include add-on combination use of empagliflozin with linagliptin and metformin. This combination has already been reviewed and approved for the fixed dose combination product Glyxambi (empagliflozin + linagliptin) as NDS Control #188534.
In recognition of the pleiotropic effects of sodium-glucose co-transporter-2 inhibitors, a change was also made to the "Indications And Clinical Use" section of the Product Monograph to remove the clause restricting use of empagliflozin in type 2 diabetes patients with established cardiovascular disease to only those with inadequate glycemic control. The "Clinical Trials" section was revised to include information on baseline HbA1c levels in trial 1245.25.
Why was the decision issued?
The purpose of this Subsequent New Drug Submission (SNDS) was to add a new indication for Jardiance (empagliflozin) to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) when used in combination with metformin and linagliptin (Trajenta) when diet and exercise plus metformin do not provide adequate glycemic control.
The new proposed indication for Jardiance is based on the efficacy and safety data from Study 1275.9; a trial that was reviewed by Health Canada at the time of the NDS for Glyxambi (fixed dose combination of empagliflozin and linagliptin). Therefore, no new data were submitted and the purpose of this SNDS is to incorporate content from the Product Monograph (PM) for the fixed dose combination of empagliflozin plus linagliptin into the Product Monograph for Jardiance (single entity empagliflozin). The new content in the Jardiance PM is consistent with that already approved for the Glyxambi Product Monograph.
The efficacy results presented from the previously evaluated trial 1275.9 support the use of empagliflozin as add-on therapy to linagliptin and metformin in patients with T2DM mellitus and insufficient glycemic control. The assessment of safety did not reveal any concerns for treatment with empagliflozin as add-on to linagliptin and metformin. The data is supportive of safe and efficacious use of empagliflozin when added to linagliptin and metformin.
Additionally, the wording of the indication for "add-on combination in patients with established cardiovascular disease" in the Jardiance PM was also revised. Based on clinical data of the EMPA-REG cardiovascular outcome, the sponsor proposes to remove the restriction for patients "who have inadequate glycemic control" from the indication. This change is acceptable because it is recognised that sodium-glucose co-transporter inhibitors (SGLT-2) have pleiotropic effects that may have benefit in cardiovascular risk reduction even in patients with type 2 diabetes who have adequate glycemic control. Furthermore, physicians might want to prescribe empagliflozin as an alternative to currently administered antihyperglycemic medications that do not have demonstrated benefits on cardiovascular death. The overall benefit and risks conclusions for empagliflozin remain positive.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.