Ipsen, a global biopharmaceutical group, announced that its partner Roche announced the implementation of a risk mitigation plan in the taspoglutide phase III programme. Taspoglutide, the first once weekly glucagon-like peptide-1 (GLP-1) analogue based on a human sequence, originating from Ipsen’s research is developed by Roche. This compound is similar to the natural hormone GLP-1 which has a key role in blood sugar regulation.

In the phase III studies, the incidence of hypersensitivity reactions reported as related to taspoglutide is higher than expected for the study population, although it remains uncommon (i.e. incidence < 1%). The most frequently reported symptoms in patients who developed hypersensitivity reactions were skin reactions and gastrointestinal symptoms, while cardiovascular and respiratory symptoms were less frequent. All patients recovered without complications.

Roche has identified a potential association between hypersensitivity reactions and anti-drug antibodies (ADAs). In consultation with the Food and Drug Administration (FDA), Roche has decided to implement a risk mitigation plan, which has been communicated to Health Authorities globally. The plan is designed to identify patients at potential risk of these reactions. As such, ADA levels will be routinely monitored and patients that develop pre-specified ADA levels will discontinue treatment and continue to be monitored in the trials. The continued safety of patients in the clinical development programmes remains the highest priority for Roche. Roche is committed to working with Health Authorities globally to continue the development of taspoglutide to meet the needs of patients with type 2 diabetes. Roche is investigating the cause of the hypersensitivity reactions and testing specific means to resolve this issue. The impact of this plan on the project and in particular on the timelines for regulatory filing are currently being assessed, however, a minimum of 12 to 18 months delay is anticipated.

Roche looks forward to sharing with the medical community at the forthcoming American Diabetes Association, data from five phase III trials demonstrating that taspoglutide delivered combined benefits of consistent robust glycemic control, across a wide spectrum of patients versus exenatide, sitagliptin and even the highest dose of insulin glargine used in a development programme. In addition, taspoglutide was associated with a low risk of hypoglycaemia and clinically important weight loss. Over the next few weeks, Roche also expects to get the headline data on the 52-week extended trials.

The T-emerge phase III clinical trial programme is designed as multicenter, multi-country, randomized, controlled (active or placebo), double-blind and open studies. Over 6,000 patients have been enrolled in the eight studies that comprise the T-emerge programme. Studies include two parallel taspoglutide arms including 10 mg once weekly and 10 mg once weekly titrated up to 20 mg once weekly after four 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 mellitus, the fourth leading cause of death in most developed countries. 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.

Roche exercised its licensing option for taspoglutide from Ipsen in 2006 and acquired exclusive worldwide rights to develop and market taspoglutide, except in Japan where these rights are shared with Teijin and in France where Ipsen has elected to retain co-marketing rights.