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New Roche/Ipsen diabetes drug shows promising efficacy
 
 
  28 June 2010
pharmatimes.com
 
Taspoglutide, Roche and Ipsen's once-weekly investigational human glucagon-like peptide analogue for type 2 diabetes appears to be at least as good for glucose control and typically better on weight loss than its competitors, researchers announced at the American Diabetes Association meeting in Orlando.
 
Three head-to-head 24-week comparisons against Eli Lilly/Amylin's GLP-1 analogue Byetta (exenatide), Merck & Co's dipeptidyl peptidase-4 inhibitor Januvia (sitagliptin) and Sanofi-Aventis' Lantus (insulin glargine) found that treatment with taspoglutide showed superior efficacy against Januvia and Byetta and at least comparable efficacy against a high dose of Lantus. Two additional Phase III studies showed that taspoglutide, when used alone or added to metformin, significantly reduced HbA1c and body weight with a low risk of hypoglycaemia. Further pre-clinical studies presented at ADA suggest that taspoglutide may help restore a normal insulin response as well as potentially preserving insulin-producing beta cells and subsequently protect them from cell death.
 
Commenting on the results presented from the studies in Roche?s T-emerge clinical trial programme, which involves over 6,000 patients, here at the ADA, Melanie Davies, professor of diabetes medicine at the University of Leicester, said they are "impressive because of the drugs chosen as comparators. Taspoglutide is of interest in context of the many treatments available to treat type 2 diabetes because it is a once-weekly therapy. The other GLP-1 analogues currently available are either once-daily or twice daily."
 
Prof Davies, who has worked on a number of diabetes treatment trials, said the efficacy of taspoglutide looked "particularly good" for the 20mg dose. The studies looked at both a 10mg and a 20mg weekly dose of taspoglutide, which is administered once a week with a pre-filled, disposable syringe with a small-gauge needle.
 
The most common adverse events seen with taspoglutide based on the 24-week data were related to gastrointestinal tolerability and injection site reactions. Prof Davies said: "GI tolerability is an issue with this class of drug. The tolerability data for taspoglutide at the higher dose did suggest GI events might be a bit higher than some comparators but we need more data to understand this better. Most of the nausea wasn?t persistent and this is the important point for clinical practice."
 
The T-emerge 4 trial results were presented by ADA President of Medicine and Science Richard Bergenstal from the International Diabetes Center in Minneapolis. This study enrolled 1,034 type 2 diabetes patients inadequately controlled on metformin alone. The patients were randomized to 24 weeks of taspoglutide 10 or 20mg once weekly, sitagliptin at 100mg per day or placebo. The primary endpoint, change in HbA1c, was significantly greater with both taspoglutide doses than with placebo or sitagliptin (-1.23% with 10 mg and -1.30% with 20mg versus -0.10% and -0.89, respectively). Weight fell 2.6kg from baseline with the higher taspoglutide dose and 1.8kg with the 10 mg dose compared with 0.9kg with sitagliptin and 0.5kg with placebo. About a quarter of patients on 20mg taspoglutide lost at least 5% of their baseline body weight.
 
Adverse events leading to discontinuation were higher with taspoglutide than with placebo or sitagliptin, as were nausea and vomiting rates. Dr Bergenstal said: "These GI events usually occurred only as a single episode per patient, typically on the day of initial or early injection.
 
In the T-emerge 5 study, 1,049 type 2 diabetes patients inadequately controlled on metformin plus a sulphonylurea (withdrawn before randomisation) were randomised to either 10 or 20mg of taspoglutide once weekly or insulin glargine. Both taspoglutide arms were non-inferior to basal insulin for the primary endpoint with a strong trend for superiority with the higher dose (-0.98% and -0.77% versus -0.84%).
 
In a third study, the T-emerge 2 trial, 1,189 type 2 diabetes patients inadequately controlled on metformin or a thiazolidinedione or a combination of both were randomised to open-label addition of 10 or 20 mg of taspoglutide once weekly or exenatide twice daily for 24 weeks. Both taspoglutide doses were superior to exenatide for the primary endpoint of HbA1c change (-1.31% at 10mg and -1.24% at 20mg versus -0.98mg with exenatide. Weight loss was 2.33kg with 20mg compared with 2.27kg with exenatide.
 
All three T-emerge studies have a planned extension phase of a further six months.
 
Roche recently announced the implementation of a risk mitigation plan in the Phase III programme designed to identify patients at potential risk of hypersensitivity reactions as there was a higher than expected rate though the incidence remained uncommon (< 1%). Dr Bergenstal said there were just 23 cases out of 3,000 patients, adding: "Roche is looking closely into the mechanism as this is unclear at present and taking steps to lower this risk." However, this plan will delay filing for regulatory approval of taspoglutide at a time when Lilly and Amylin have already filed for a weekly version of Byetta, called Bydureon.
 
By Rhonda Siddall in Orlando
 
 
 
 
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