Regulatory Decision Summary for GLYXAMBI

Two pivotal, randomized, double-dummy, double-blind, placebo-controlled parallel group phase 3 trials with a 16-week open label period, followed by a 24-week double-blind phase were filed in support of the proposed indications. Study 1275.9 assessed the safety and efficacy of Glyxambi as an add-on of empagliflozin on a background of metformin and linagliptin. Study 1275.10 assessed the safety and efficacy of Glyxambi as an add-on of linagliptin on a background of metformin and empagliflozin.

Study 1275.9 investigated the effect of Glyxambi in patients inadequately controlled on metformin + linagliptin 5 mg. A statistically significant and clinically meaningful benefit of metformin + Glyxambi 10/5 (10 mg empagliflozin + 5 mg linagliptin) and of metformin + Glyxambi 25/5 (25 mg empagliflozin + 5 mg linagliptin) was observed on reduction from baseline HbA1c at week 24. There was no evidence of a dose effect on efficacy or safety. Common adverse drug reactions were urinary tract infection (UTI), genital mycotic infection, lipase increased, diarrhoea and increased urination. There were no deaths and few serious or severe Adverse Events (AEs) or AEs that resulted in discontinuation of study drug.

Study 1275.10 investigated the effect of Glyxambi in patients inadequately controlled on metformin + empagliflozin 10 mg or metformin + empagliflozin 25 mg. A larger reduction from baseline in HbA1c at week 24 was shown with the combination of metformin and Glyxambi 10/5 or Glyxambi 25/5 compared to the combination of metformin and empagliflozin 10 mg or empagliflozin 25 mg, respectively. The differences were statistically significant and clinically meaningful. Common adverse drug reactions included UTI and lipase increase. There were no deaths and few serious or severe AEs or AEs that resulted in discontinuation of study drug.

In a separate supportive 52-week phase 3 study, Glyxambi 10/5 and Glyxambi 25/5 demonstrated a meaningful benefit relative to each mono component at week 24 that was sustained at week 52, in patients with T2DM inadequately controlled on metformin.

In the overall assessment of the safety data from the phase 3 clinical trials, no important new or synergistic adverse reaction was observed relative to what has been observed with each mono component.

Risk mitigation was achieved with adequate labelling of all safety issues and restriction of the indications. A Risk Management Plan was submitted to the Marketed Health Products Directorate.

Glyxambi was considered to have significant benefits on glycemic control in patients with T2DM when given in combination with metformin, with acceptable risk.