Nesina®, in Combination with Actos®

Partnership with Takeda Pharmaceuticals

Takeda is developing a combination therapeutic using Nesina® (alogliptin) and ACTOS® (pioglitazone HCl) in a single tablet for the treatment of type 2 diabetes (T2D).  In July 2011, Takeda received regulatory approval from Japan's Ministry of Health, Labour and Welfare for the Nesina and ACTOS combination and it is now being sold in Japan under the brand name LIOVEL®.

Takeda has resubmitted a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) for the Nesina and ACTOS combination therapeutic, and the Prescription User Fee Act (PDUFA) action date has been set for April 25, 2012.  If approved, this will be the first T2D treatment option that includes a DPP-4 inhibitor and a thiazolidinedione, or TZD. Furiex will be entitled to receive royalties on product sales.

Actos

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.

In an initial study, potential pharmacokinetic (PK) drug-drug interactions of alogliptin with pioglitazone or glyburide were evaluated in healthy adults in a randomized, six-sequence, three-period crossover study. Participants received once-daily alogliptin with pioglitazone or glyburide (combination), or alogliptin alone (monotherapy). Minor changes in PK parameters between combination therapy and monotherapy were obtained but not judged to be clinically relevant. The combination treatments were well-tolerated, although glyburide frequently caused hypoglycemia. Most adverse events were of mild intensity and occurred with a frequency similar to that with monotherapy. It was concluded that pioglitazone or glyburide can be administered with alogliptin without dose adjustment to any component of the combination therapy. [1]

Alogliptin was tested for efficacy and safety in patients with T2D inadequately controlled by therapy with a TZD. In a multicenter, double-blind, placebo-controlled clinical study, 493 patients 18-80 years old with inadequate glycemic control after stabilization despite ongoing treatment with a TZD were randomly assigned to treatment once daily with pioglitazone and 12.5 mg or 25 mg alogliptin or placebo. Concomitant therapy with metformin or sulfonylurea at prestudy doses was permitted. The results indicated that the addition of alogliptin to pioglitazone therapy significantly improved glycemic control in patients with T2D and was generally well-tolerated. [2]

Alogliptin clinical trials can be accessed at www.clinicaltrials.gov.

References

  1. Karim et al. Clin Pharmacol. 2009 Oct.; 49(10): p. 1210-9.
  2. Pratley et al., Curr Med Res Opin. 2009 Oct.; 25(10): p. 2361-71.