Positive results from Phase III trials with two type 2 diabetes candidates, dapagliflozin and lixisenatide, were separately reported by their developers at the recent 46th European Association for the Study of Diabetes (ESAD) annual meeting. With the future of GlaxoSmithKline’s marketed type II diabetes drug Avandia® up in the air, positive late-stage clinical data on new treatments for the disorder are bound to arouse interest within the industry.
Sanofi-aventis said the first Phase III data to emerge from its GetGoal clinical trial program with lixisenatide showed that once-daily administration of the drug as monotherapy led to significant reductions in glycosylated hemoglobin (HbA1c) levels and effectively controlled postprandial glucose. Bristol-Myers Squibb (BMS) and partner AstraZeneca separately reported that adding their investigational drug dapagliflozin to existing therapy with glimepiride resulted in better reductions in HbA1c levels than glimepiride alone.
Sanofi-aventis’ lixisenatide is a once-daily injectable GLP-1 receptor agonist, which is in development both as monotherapy and for use in combination with basal insulin and long-acting insulin analogues. The 12-week Phase III monotherapy trial reported at ESAD involved 361 type 2 diabetes patients not currently receiving glucose-lowering therapy. Data from the trial showed that in comparison with patients receiving placebo, a significant number of those given lixisenatide demonstrated HbA1c levels less than or equal to 6.5%. Lixisenatide therapy also significantly reduced the mean change in glucose levels from baseline two hours after a meal by up to -5.5 mmol/L. Treatment with the active drug was separately shown to reduce glucose excursion by up to -4.36 mmol/L. All treatment groups demonstrated weight loss as a result of therapy, sanofi-aventis points out.
The firm’s flagship diabetes 1 and 2 therapy, Lantus®, also featured at ESAD, was its top selling pharmaceutical in 2009, achieving sales of €3.08 billion (about $3.92 billion), up 22.5% on 2008 at constant exchange rates.
BMS and AstraZeneca’s dapagliflozin candidate is a sodium-glucose co-transporter-2 (GSLT2) inhibitor currently in Phase III trials as a once-daily oral therapy for type 2 diabetes. The 24-week Phase III study reported at ESAD evaluated the efficacy of different doses of dapagliflozin as add-on therapy to glimepiride in 597 patients who exhibit inadequate glycemic control when receiving at least half the maximal recommended dose of glimepiride monotherapy.
Results showed that adding dapagliflozin to glimepiride therapy resulted in dose-dependent reductions from baseline of HbA1c of up to -0.82%. Patients receiving dapagliflozin also demonstrated dose-dependent weight loss effects of up to -2.26 kg and dose-dependent reductions from baseline in the oral glucose tolerance test of up to -34.9 mg/dL. Additional data showed that up to 31.7% of patients in the dapagliflozin groups achieved an HbA1c level of less than 7% at week 24.
BMS’ marketed oral type 2 diabetes therapy, Onglyza (saxagliptin), has also been developed in collaboration with AstraZeneca. The dipeptidyl peptidase-4 inhibitor is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. First sanctioned in the U.S. in 2009 and with approvals in over 36 worldwide, it achieved sales of $38 million in the first six months of this year, BMS reports.
While GSK waits for regulatory authorities to decide on the future of Avandia the firm continues to counter the ever-increasing wave of adverse reporting on its drug. However, research at the U.K.-based drug giant on new treatments to diabetes 2 continues. Pipeline products include a glucagon-like peptide 1 agonist Syncria, which started in Phase III development in early 2009. The Phase II pipeline includes an SIRT1 activator, a GPCR 119 agonist, and a glycogen phosphorylase inhibitor. An SLGT1 inhibitor is currently undergoing Phase I evaluation.