GLP-1 Once-Weekly Analogue Taspoglutide Found Safe and Effective

Roche has disclosed results of the phase III T-emerge 3 study in patients with diabetes with taspoglutide, the first once weekly glucagon-like peptide-1 (GLP-1) analogue based on a human sequence.

The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone.

The results of T-emerge 3 showed that taspoglutide demonstrated superiority in HbA1c change versus placebo following 24 weeks of treatment. The study analysis included 326 patients, randomized into three arms (taspoglutide 10 mg once weekly, taspoglutide 20 mg once weekly and placebo). In this study taspoglutide was generally well tolerated and the most frequently reported adverse events among taspoglutide treated patients were nausea and vomiting.

In addition to the already released T-emerge 1, T-emerge 2, T-emerge 4, T-emerge 5 and T-emerge 7 studies, data from T-emerge 3 will be submitted for presentation at upcoming international scientific meetings. A further two T-emerge Phase III trials exploring taspoglutide in patients with diabetes are ongoing.

T-emerge 3 is a combination therapy (add-on to metformin and pioglitazone), double-blind, placebo-controlled, 24-week core study, to demonstrate superiority versus placebo, involving 326 patients equally randomised into three arms (taspoglutide at doses of 10 mg and 20 mg once weekly, and placebo). All patients continue into the 28-week long-term extension on taspoglutide.

Roche's T-emerge Phase III clinical trials are designed as multicenter, multi-country, randomized, controlled (active or placebo), double-blind and open studies. Over 6,000 patients will be enrolled in the eight studies that comprise the T-emerge program. Studies include two parallel taspoglutide arms including 10 mg once weekly and 10 mg once weekly titrated up to 20 mg once weekly after 4 weeks. Four of the eight studies have active comparators, including exenatide, sitagliptin, insulin glargine and pioglitazone.

Taspoglutide was selected from a family of human once-weekly long-acting glucagon-like peptide-1 (GLP-1) analogues with structural modifications which confer intrinsic controlled release properties. Ipsen is the originator of the concept of matrix free sustained release formulation applied to therapeutic peptides and proteins. Taspoglutide is being developed, by Roche, as a novel and innovative treatment for patients with Type 2 diabetes. The structure of the molecule is similar to that of the natural human hormone GLP-1, and has the potential for intervals of up to two weeks in between administration without the use of a matrix.

From the results it was concluded that taspoglutide was safe, well-tolerated at high doses and efficacious for lowering HbA_1c. Up-titration of dose was not associated with a worsening AE profile.

Diabetic Medicine, Volume 27 Issue 5 Pages 556-562 Feb. 10, 2010