One day after recommending approval of the diabetes combo drug IDegLira (Novo Nordisk), the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) has voted 12 to 2 for approval of the new drug application (NDA) for iGlarLixi (Sanofi), a fixed-ratio combination of basal insulin glargine 100 units/mL (Lantus) and an investigational glucagon-like peptide-1 (GLP-1) receptor agonist, lixisenatide, for the treatment of adults with type-2 diabetes (T2D).
The FDA is not obliged to follow the advice of its advisory panels, but it typically does so.
The NDA submission for iGlarLixi was based on data from two phase 3 studies, which enrolled more than 1,900 adults worldwide to evaluate the efficacy and safety of the fixed-ratio combination of basal insulin glargine 100 units/mL and GLP-1 receptor agonist lixisenatide when used in patient populations insufficiently controlled after oral antidiabetic agents and after basal insulin therapy, respectively. Both studies met their primary endpoints.
An NDA was also submitted for lixisenatide alone. This submission was based on results from the GetGoal clinical program, which included 13 trials involving more than 5,000 adults with T2D. It also included findings from the ELIXA study, a long-term cardiovascular (CV) outcomes trial in adults with T2D and a high CV risk (i.e., patients who had recently experienced a spontaneous acute coronary syndrome event).
According to briefing data supplied to the FDA, lixisenatide lowers blood glucose through three different mechanisms: stimulation of insulin secretion when blood glucose levels rise; inhibition of postprandial glucagon secretion; and delayed gastric emptying leading to decreased glucose absorption after a meal, with a resultant reduction in postprandial glucose (PPG) excursions. The mechanisms of action of lixisenatide and insulin glargine are complementary: insulin glargine lowers basal glucose levels throughout the day while lixisenatide primarily targets PPG excursions.
Approval decisions on iGlarLixi and lixisenatide are anticipated in July and August 2016, respectively. Lixisenatide is currently approved in more than 60 countries worldwide under the proprietary name Lyxumia.
Despite its positive vote, the FDA panel expressed concern about the possibility of dosing errors related to the way iGlarLixi is labeled. The panel also had major issues with the way the proposed pen devices are designed. Trial data included evidence that some patients had trouble using the pens.