Regulatory Decision Summary for Steglujan
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 New Drug Submission (NDS) was filed to obtain marketing authorization for the use of Steglujan (ertugliflozin and sitagliptin) immediate release fixed-dose combination (FDC) tablets to improve glycemic control in adult patients with type 2 diabetes mellitus
a) for whom metformin is inappropriate due to contraindications or intolerance
b) who are inadequately controlled on metformin
c) who are inadequately controlled on metformin and either sitagliptin or ertugliflozin, and
d) who are inadequately controlled on metformin and sitagliptin.
The approved use is for combination with metformin to achieve glycemic control in adult patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin, or those already controlled with metformin, sitagliptin and ertugliflozin, as individual components.
Why was the decision issued?
Steglujan is a FDC of ertugliflozin 5 mg or 15 mg with sitagliptin 100 mg (5/100 mg and 15/100 mg doses, respectively). These agents act to reduce hyperglycemia via separate mechanisms of action. The proposed Steglujan FDC tablets were not used in Phase III clinical studies. The approval of Steglujan is requested based in part on a pivotal comparative bioavailability study bridging the proposed product to its individual components, ertugliflozin and sitagliptin (already approved drugs in Canada).
Pivotal Phase III study P006/1015 was a randomized, double blind, multicenter, placebo-controlled, phase 3 trial supporting the approved indication, which assessed the safety and efficacy of the addition of ertugliflozin to a background of sitagliptin and metformin. Study P006/1015 demonstrated statistically significant and clinically meaningful changes (placebo-adjusted) from baseline in the percentage of glycated hemoglobin (HbA1c) of -0.69 and -0.76 for the 5/100 mg and 15/100 mg Steglujan doses, respectively. Reductions in fasting plasma glucose, body weight, and sitting systolic blood pressure, and those who achieved a target HbA1c of <7% at week 26 (key secondary endpoints) were supportive of the primary endpoint. Primary and secondary endpoint analyses of supportive Phase III trials P005/1019 and P017/1047 were consistent with that of the pivotal study. P005/1019 further demonstrated that the combination of ertugliflozin and sitagliptin was statistically superior to either of the individual components.
Common treatment-related adverse events (AEs) in patients treated with ertugliflozin and sitagliptin on a background of metformin were genital mycotic infections. There were no deaths and few serious or severe AEs that resulted in discontinuation of the study drug. In the overall assessment of the safety data from the phase 3 clinical trials, no important new or synergistic AEs were observed with Steglujan relative to what has been observed with each component as a single agent.
Risk mitigation was achieved with adequate labelling of all safety issues, restriction of the indication, and assessment of the Risk Management Plan by the Marketed Health Products Directorate.
The Steglujan FDC product offers a convenient dosing option over the separate administration of each individual component, thereby potentially improving patient compliance.
The benefit/harm/uncertainty assessment of Steglujan when used as indicated is positive.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.