Basal Insulin Peglispro Superior to Insulin Glargine in Phase III Studies
New drug application expected in early 2015
Basal insulin peglispro (BIL, Eli Lilly) demonstrated statistically significant lower hemoglobin A1c (HbA1c) levels compared with insulin glargine (Lantus, Sanofi-Aventis) at 26 weeks and 52 weeks, respectively, in the IMAGINE-1 and IMAGINE-3 phase III clinical trials in patients with type-1 diabetes. The patients in these studies were also taking mealtime insulin.
Patients in the IMAGINE-1 study continued treatment beyond 26 weeks, and the HbA1c superiority for BIL was maintained at 52 and 78 weeks.
A new drug application is expected to be filed with the FDA by the end of the first quarter of 2015.
The primary efficacy endpoint of non-inferior HbA1c compared with insulin glargine was met in both the IMAGINE-1 and IMAGINE-3 trials, which also demonstrated superiority. In addition, significantly more patients taking BIL compared with those taking insulin glargine achieved an HbA1c level of less than 7% — a target for glycemic control established by the American Diabetes Association.
Both studies also showed that the rate of nocturnal hypoglycemia was significantly lower in patients taking BIL than in those taking insulin glargine. In both trials — in which patients were taking both mealtime and basal insulin — there was a statistically significant increase in the rate of total hypoglycemia for patients taking BIL compared with those taking insulin glargine because of a higher rate of daytime hypoglycemic events. In the open-label IMAGINE-1 trial, patients taking BIL reported a statistically significant higher rate of severe hypoglycemic events. However, in the larger, blinded IMAGINE-3 trial, the rate of severe hypoglycemic events with BIL was numerically lower compared with that of insulin glargine, but was not statistically significant.
Patients taking BIL experienced changes in lipid parameters, including a small but statistically significant increase in triglycerides, in both trials. In the IMAGINE-3 trial, there were small but statistically significant reductions and increases, respectively, in high-density lipoprotein cholesterol (HDL-C) and in low-density lipoprotein cholesterol (LDL-C) in patients taking BIL compared with those taking insulin glargine. Moreover, IMAGINE-3 showed that patients taking BIL experienced small but statistically significant increases in systolic and diastolic blood pressure compared with those taking insulin glargine (a mean difference of less than 2 mm Hg at 52 weeks). Statistically significant differences in HDL-C and LDL-C and in blood pressure were not observed in IMAGINE-1.
In both trials, significantly more injection-site reactions occurred in patients taking BIL compared with those taking insulin glargine.
In the core phase III clinical trial program for BIL — consisting of seven IMAGINE trials in patients with type-1 or type-2 diabetes — the superiority of BIL in reducing HbA1c was established in all six of the studies conducted against active comparators.
Source: Eli Lilly; September 4, 2014.