Takeda receives positive CHMP opinion for three new type 2 diabetes therapies, VipidiaTM (alogliptin) and fixed-dose combinations VipdometTM (alogliptin-metformin) and IncresyncTM (alogliptin-pioglitazone)

Takeda Pharmaceutical Company Limited (Takeda) today announced that the Committee for Medicinal Products for Human Use (CHMP), of the European Medicines Agency (EMA), has issued a positive opinion for VipidiaTM (alogliptin), a dipeptidyl peptidase IV (DPP-4) inhibitor, and for the fixed dose combination (FDC) therapies VipdometTM (alogliptin-metformin) and IncresyncTM (alogliptin-pioglitazone) for the treatment of type 2 diabetes patients who are uncontrolled on existing therapies.1,2

“The number of people at risk from complications associated with type 2 diabetes continues to rise across Europe as many still fail to reach treatment goals,” said Trevor Smith, Head of Commercial Operations, Europe & Canada, Takeda Pharmaceuticals. “This positive opinion marks an important milestone in Takeda’s ongoing commitment in working to advance patient care and helping to meet the individual needs of this growing patient population.”

The CHMP opinion was based on data from a robust clinical trial programme involving more than 11,000 patients treated for up to four years, and two key studies, the one year data from the ENDURE[1] trial and interim data from the cardiovascular outcomes trial EXAMINE[2].

The efficacy of alogliptin was studied as an adjunct to diet and exercise as an add-on therapy to several other classes of anti-diabetic medications, including metformin, pioglitazone, insulin and sulfonylureas (SUs). In these studies alogliptin 25mg tablets taken once-daily, demonstrated clinically and statistically significant reductions in HbA1c, with a good overall tolerability profile and low incidence of hypoglycemia compared with active control or placebo.2-7 It has also been shown to be weight neutral and will be available in a range of doses suitable to treat patients with all stages of renal impairment, including end stage renal disease (ESRD).2

Study results indicated that alogliptin co-administered with either metformin or pioglitazone produced significant improvements in glycemic control compared with the respective monotherapies.8-10 Fixed dose combinations of alogliptin with either metformin or pioglitazone offer the additional benefit of combining two medications in one, which may help to reduce the number of pills patients must take each day.

Common adverse events reported with alogliptin include upper respiratory tract infection, nasopharyngitis, headache, abdominal pain, gastroesophageal reflux (GERD), pruritus and rash.2 In patients treated with alogliptin co-administered with metformin, common adverse events include upper respiratory tract infection, nasopharyngitis, headache, abdominal pain, GERD, diarrhea, vomiting, gastritis, gastroenteritis, pruritus and rash.11 Common adverse events reported with patients treated with alogliptin co-administered with pioglitazone include upper respiratory tract infection, sinusitis, nausea, dyspepsia, abdominal pain, pruritus, peripheral edema and increased weight.12

“Type 2 diabetes is a complex disease to manage; no two patients are the same and each responds differently to medications. Therefore all patients require a treatment approach that is individualized to their needs,” commented Professor Jiten Vora, Consultant Physician and Endocrinologist, Royal Liverpool University Hospitals, Liverpool, UK. “Although there are a number of treatment options available, there is still a need to improve glycemic control in many patients, particularly those more complex patients with multiple co-morbidities who are taking many different medications. These new treatment options will further help clinicians to tailor treatment to individual patient needs and help to improve glycemic control.”

References

1. European Medicines Agency. Available at: http://www.ema.europa.eu/ema/. [Link to be updated in line with CHMP opinion]
2. Data on file. Takeda Pharmaceuticals International GmBH
3. DeFronzo RA, Fleck PR, Wilson CA, et al. Efficacy and safety of dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control. Diabetes Care 2008;31(12):2315-2317.
4. Nauck MA, Ellis GC, Fleck PR, et al. Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes and inadequately controlled with metformin monotherapy: a multicentre, randomised, double blind, placebo-controlled study. Int J Clin Pract 2009;63(1):46-55.
5. Pratley RE, Reusch JE-B, Fleck PR, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomised, double blind, placebo-controlled study. Curr Med Res Opin 2009;25(10):2361-2371.
6. Rosenstock J, Rendell MS, Gross JL, et al. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA1c without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab 2009;11:1145-1152.
7. Pratley RE, Kipnes MS, Fleck PR, et al. Efficacy and safety of dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes, Obesity and Metabolism 2009;11:167-176.
8. Pratley RE, Wilson CA and Fleck PR. Alogliptin plus metformin combination therapy vs alogliptin or metformin monotherapy for type 2 diabetes mellitus. Presented at the 48th Annual Meeting of the European Association for the Study of Diabetes, Berlin 2012. Poster 841-P.
9. DeFronzo RA, Burant CF, Fleck PR, et al. Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin treated patients with type 2 diabetes. J Clin Endocrinol Metab 2012; 97(5):1615-1622.
10. Bosi E, Ellis GC, Wilson CA, et al. Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52 week, randomized, double-blind, active-controlled, parallel-group study. Diabetes, Obes and Metab 2011;13(12): 1088-1096.
11. Data on file. Takeda Pharmaceuticals International GmBH
12. Data on file. Takeda Pharmaceuticals International GmBH
13. Christopher R and Karim A. Clinical pharmacology of alogliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of type 2 diabetes. Expert Rev Clin Parmacol 2009;2(6):589-600.
14. International Diabetes Federation. IDF Diabetes Atlas, 5th edition. Brussels, Belgium. Last accessed 4 April 2013, available at: http://www.idf.org/diabetesatlas.
15. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient centred approach. Position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2012;35(6):1364-1379.