Nesina® (Alogliptin)
Partnership with Takeda Pharmaceuticals
Nesina® (alogliptin) is a member of a new class of drugs for the oral treatment of type 2 diabetes (T2D). Nesina is being developed and marketed by Takeda Pharmaceuticals. In April 2010, Takeda received regulatory approval from Japan's Ministry of Health, Labour and Welfare for Nesina and it is now being sold in Japan.
Takeda has resubmitted a new drug application (NDA) with the U.S. Food and Drug Administration (FDA), and the Prescription User Fee Act (PDUFA) action date has been set for April 25, 2012.
As a result of their collaboration, Furiex has rights to royalties and sales-based milestones from Takeda for the sale of Nesina in Japan. Furiex will be entitled to receive regulatory milestones, royalties and sales-based milestones upon marketing approval of Nesina in other countries.
Alogliptin is a DPP-4 inhibitor that slows the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), which play a major role in regulating blood glucose levels and have the potential to improve pancreatic beta-cell function.
Alogliptin was tested in 329 drug-naïve patients with inadequately controlled T2D in a double-blind, placebo-controlled, multicenter study. Patients were randomized to once-daily treatment with 12.5 mg or 25 mg alogliptin or placebo for 26 weeks. The primary efficacy end point was HbA(1c). Alogliptin was well-tolerated and significantly improved glycemic control in these patients with T2D without raising the incidence of hypoglycemia. [1]
Alogliptin was tested for efficacy and safety in elderly (65 or older) and younger patients with T2D. The patients received 12.5 mg or 25 mg alogliptin or placebo for 26 weeks. The studies evaluated alogliptin alone and co-administered with pioglitazone, glyburide, metformin or insulin. A pooled analysis was done on the elderly patients of six randomized, double-blind, placebo-controlled studies. Alogliptin was found to be effective and well-tolerated in the elderly patients enrolled in these studies. Improvements in HbA(1c) were similar to those seen in younger patients, and no increase in the risk of hypoglycemia, weight gain or other adverse events was apparent in elderly patients. [2]
Initial clinical trials were conducted to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) and tolerability profiles and explore the efficacy of multiple oral doses of alogliptin in patients with T2D in a randomized, double-blind, placebo-controlled, parallel-group study. Patients with T2D between the ages of 18 and 75 years were assigned to receive a single oral dose of alogliptin 25 mg, 100 mg or 400 mg or placebo (4:4:4:3 ratio) once daily for 14 days. The study assessed PK profiles, plasma DPP-4 inhibition, tolerability and efficacy end points, plasma glucose, HbA(1c), C-peptide and fructosamine values. The results indicated that in these adult patients with T2D, alogliptin inhibited plasma DPP-4 activity and significantly decreased plasma glucose levels. A once-daily dosing regimen was supported by the PK and PD profiles. Alogliptin was generally well-tolerated, with no dose-limiting toxicity. [3]
Alogliptin clinical trials can be accessed at www.clinicaltrials.gov.
T2D is a chronic condition that is becoming an epidemic due to greater prevalence of sedentary and urbanized lifestyle. The World Health Organization predicts that approximately 4 percent of the world population will have diabetes by 2030. The worldwide anti-diabetic market was estimated at $30 billion in 2009 with DPP-4 inhibitors making up approximately $3 billion.
References
- DeFronzo et al., Diabetes Care. 2008 Dec.; 31(12): p. 2315-7.
- Pratley et al., J Am Geriatric Soc. 2009 Nov.; 57(11): p. 2011-9.
- Covington et al., Clin Ther. 2008 March; 30(3): p. 499-512