As for whether the ELIXA trial represents a high-quality study with believable results and an important endpoint, “the answer is a resounding yes,” he said.
Lixisenatide was approved in Europe in 2013 for the treatment of adults with type 2 diabetes mellitus to achieve glycemic control in combination with oral glucose-lowering medical products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycemic control.
According to Sanofi, a New Drug Application for lixisenatide is on track to be resubmitted to the Food and Drug Administration in the third quarter of 2015. An initial application was accepted for review in 2013, but Sanofi delayed the approval process based on concerns regarding cardiovascular risk. The application to be resubmitted later this year will include findings from the GetGoal Duo-2 clinical trial, which were reported in a poster at the ADA meeting; all coprimary endpoints in the 26-week, randomized, open-label trial were met, reported Dr. Julio Rosenstock, director of the Dallas Diabetes and Endocrine Center.
In GetGoal Duo-2, lixisenatide was compared as a once-daily 20 mcg add-on to optimally titrated insulin glargine with or without metformin vs. the addition of rapid-acting insulin glulisine with or without metformin injected once daily at the time of the patient’s main meal (basal-plus), or three times daily at meal time (basal-bolus). Subjects were adults with poorly controlled diabetes on basal insulin with or without oral antidiabetic drugs for at least 6 months.
In 890 patients included in an intention-to-treat analysis, lixisenatide was noninferior to both comparator insulin regimens for reducing HbA1c levels (mean difference, –0.05% vs. basal plus and 0.21% vs. basal bolus), and was shown to be statistically superior to basal-bolus for body weight change (mean difference, –2 kg), Dr. Rosenstock said.
Postprandial glucose also was significantly reduced with lixisenatide vs. both insulin glulisine regimens (mean difference, –37 mg/dL vs. basal plus and –40 mg/dL vs. basal bolus), as was hypoglycemia (estimated rate ratios, 0.8 and 0.5, respectively).
Nausea occurred in 25% of the lixisenatide patients vs. 1% and 2% of the basal plus and basal bolus patients, respectively, and vomiting and diarrhea occurred in 9% and 7%, respectively, of the lixisenatide patients.
Both lixisenatide studies were sponsored by Sanofi. Dr. Pfeffer reported receiving honoraria and/or research grants from, or serving as a consultant for, Aastrom, Amgen, Bristol-Myers Squibb, Celladon, Concert, Hamilton Health Sciences, Keryx, Medtronic, Merck, Novartis, Roche, Sanofi-Aventis, Servier, Teva, University of Oxford, and Xoma. The Brigham and Women’s Hospital has patents for the use of inhibitors of the renin-angiotensin system in survivors of MI with Novartis.