Lixisenatide is a potent and highly selective GLP-1 peptide agonist, for once-daily injectable dosing to treat type 2 diabetes.
Sanofi, which is developing Lixisenatide both in a stand-alone pen device ( Lyxumia ) and in a combination pen with Lantus, an Insulin product.

Lixisenatide has been evaluated in an extensive global phase III program, GetGoal, which comprised several studies and involved more than 4,500 patients with type 2 diabetes.

In October 2011, Sanofi filed a Marketing Authorisation Application ( MAA ) with the European Medicines Agency ( EMA ) for the regulatory approval of Lixisenatide as a novel treatment for type 2 diabetes. The MAA includes documentation from the completed GetGoal Phase III program, providing substantial data to support Lixisenatide’s intended use as a novel treatment of adults with type 2 diabetes to achieve glycemic control: a ) in combinations with oral medication ( in patients failing to achieve glycemic control on oral anti-diabetes drugs ); and in combination with basal Insulin ( in patients not sufficiently controlled on basal Insulin alone ).

To date, top-line results have been reported for Lixisenatide from the GetGoal-Mono study ( Lixisenatide as monotherapy in drug naïve patients ), the GetGoal-S, GetGoal-F1, GetGoal-M and Get-Goal-P studies ( evaluating Lixisenatide as add-on to oral anti-diabetes treatment ), GetGoal-X ( comparing Lixisenatide to Exenatide, a marketed GLP-1 agonist ), and the GetGoal-L and GetGoal-L Asia ( evaluating Lixisenatide as add-on to basal Insulin ) studies.
In all the studies, Lixisenatide has delivered positive results meeting the primary endpoint of blood glucose lowering ( measured on HbA1c ) and with consistent HbA1c reduction across studies, driven by an effective reduction of fasting blood glucose levels and a pronounced lowering of post-prandial glucose.

Further, a beneficial effect in body weight has been observed across the studies. Lixisenatide once-daily, with a one-step dose increase regimen and a single maintenance dose, has also been shown to be well-tolerated and to lead to significantly improved glycemic control with low risk of hypoglycemia in the overall GetGoal program.
As with other members of the GLP-1 drug class, nausea and vomiting were the most commonly reported adverse events in most studies, albeit mild and transient.

Top-line results have been reported also from a phase IIIb study, GetGoal Duo 1, evaluating the efficacy and safety of Lixisenatide in a free combination with Lantus ( Insulin glargine ) in type 2 diabetes patients uncontrolled on oral anti-diabetes drugs, mainly Metformin.
The results were positive, showing that Lixisenatide in combination with Lantus helped to achieve HbA1c target levels less than 7.0% in patients with uncontrolled HbA1c despite well controlled fasting glucose levels.
In the study, Lixisenatide showed to significantly improve 2-hour post-prandial glucose.
The most common adverse events were mild and transient nausea and vomiting. 50 ( 22.4% ) Lixisenatide treated patients and 30 ( 13.5% ) patients on placebo reported symptomatic hypo-glycemic events as defined in the protocol.

Sanofi is also conducting a large cardiovascular safety outcome study, named ELIXA, with the primary objective to evaluate the cardiovascular risk profile of Lixisenatide in up to 6,000 type 2 diabetes patients with a history of a cardiac event, such as a myocardial infarction or unstable angina.

Source: Zealand Pharma, 2012

XagenaMedicine2012