Takeda receives European marketing authorisation for three new type 2 diabetes therapies

Takeda Pharmaceutical Company Limited (Takeda) today announced that the European Commission has granted Marketing Authorisation (MA) for Vipidia^TM ( alogliptin), a dipeptidyl peptidase IV (DPP – 4) inhibitor, for the treatment of type 2 diabetes patients who are uncontrolled on existing therapies^{1 – 3} and for the fixed – dose combination (FDC) therapies Vipdomet^TM (alogliptin with metformin) and Incresync^TM (alogliptin with pioglitazone). The Committee for Medicinal Products for Human Use (CHMP), of the European Medicines Agency (EMA), issued a positive opinion for these products on July 26, 2013.

This announcement comes shortly after publication of final results from the cardiovascular (CV) safety outcomes trial EXAMINE* in The New England Journal of Medicine (NEJM).¹ Alogliptin is the first agent for the treatment of type 2 diabetes to be licensed with demonstrated CV safety outcomes data.⁴

“The incidence of type 2 diabetes in Europe is on the rise with an estimated 55 million cases in 2011 predicted to increase to an estimated 64.2 million in 2030” said Trevor Smith, Head of Commercial Operations, Europe & Canada, Takeda . “We know that many people living with type 2 diabetes struggle to manage their disease so there is a need for new therapies to assist them in doing so. This Marketing Authorisation marks an important milestone in Takeda’s ongoing commitment in working to a dvance patient care and helping to meet the individual needs of this growing patient population .”

The MA was based on data from a robust clinical trial program involving more than 11,000 patients treated for up to four years and two key studies the ENDURE^† trial and interim data from the cardiovascular safety outcomes trial EXAMINE.

Results from the ENDURE study demonstrate d that alogliptin 25mg in addition to metformin offered superior durability of glycemic control at two years with notably fewer hypoglycemic episodes and no negative impact on weight compared to a sulphonylurea (SU) , (glipizide).⁵ Results also showed that when alogliptin was given in combination with metformin, significantly more patients achieve target HbA_1c of ≤ 7% compared with an SU in combination with metformin.⁵

The efficacy of alogliptin was also studied as an adjunct to diet and exercise as an add-on therapy to several other classes of anti-diabetic medications, including metformin, thiazolidinediones (TZDs), insulin and SUs. In these studies alogliptin 25mg tablets taken once daily, demonstrated clinically and statistically significant reductions in HbA_1c, with a good overall tolerability profile and low incidence of hypoglycemia compared with active control or placebo.^{1, 6-10} Previous trials indicated that alogliptin co-administered with either metformin or pioglitazone produced significant improvements in glycemic control compared with the respective monotherapies.^11-13

Common adverse events reported with alogliptin include upper respiratory tract infection, nasopharyngitis, headache, abdominal pain, gastroeosophageal reflux (GERD), pruritus and rash.¹ 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.² 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.³

“Although there are a number of treatment options already available, many patients still fail to meet glycemic targets, experience hypoglycemic episodes, are overweight and remain at risk from long-term complications, such as cardiovascular disease and renal impairment,” commented Professor Simon Heller, Professor of Clinical Diabetes at the University of Sheffield, Sheffield, UK and EXAMINE trial investigator. “ Today’s announcement, along with the cardiovascular outcomes data from EXAMINE, means that physicians within the European Union will have access to a comprehensive range of new treatments to help eligible patients manage their disease. Flexible treatments that are convenient for patients and that can help to control the numerous and complex factors associated with type 2 diabetes, may be of value in helping to implement a more personalised approach to care.”

Alogliptin is available in a range of doses suitable to treat patients with all stages of renal impairment, including end stage renal disease (ESRD).¹ Takeda received approval for alogliptin (Nesina ) in 2010 and in fixed-dose combination with pioglitazone (Liovel) in 2011 in Japan. In the US, Takeda received approval for alogliptin as a monotherapy (Nesina) and in fixed-dose combinations with metformin (Kazano) and with pioglitazone (Oseni) in 2013. In addition, alogliptin was approved in China in 2013. The approval of these MAs will not require any change of the outlook for Takeda’s consolidated results for the full year of fiscal 2013 announced on July 31, 2013.

References

1. Summary of product characteristics for Vipidia . Takeda Pharmaceuticals GmBH.
2. Summary of product characteristics for Vipdomet. Takeda Pharmaceuticals GmBH.
3. Summary of product characteristics for Incresync. Takeda Pharmaceuticals GmBH.
4. White, W.B. et al. (2013) Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. The New England Journal of Medicine. [online] nejm.org. Available from: http://www.nejm.org/doi/full/10.1056/ NEJMoa1305889
5. Del Prato S, Camisasca R et al. Durability of the Efficacy and safety of Alogliptin Compared to Glipizide over 2 Years When Used in Combination with Metformin. Poster #66 – LB presented at the 73rd Scientific Sessions of the American Diabetes Association (ADA), Chicago, Illinois, June 21 – 25, 2013.
6. 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.
7. 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, rando mised, double blind, placebo – controlled study. Int J Clin Pract 2009;63(1):46 – 55.
8. 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 ran domised, double blind, placebo – controlled study. Curr Med Res Opin 2009;25(10):2361 – 2371.
9. 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.
10. 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, O besity and Metabolism 2009;11:167 – 176.
11. 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 48 th Annual Meeting of the European Association f or the Study of Diabetes, Berlin 2012. Poster 841 – P.
12. 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 Met ab 2012; 97(5):1615 – 1622.
13. 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.
14. 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.
15. International Diabetes Federation. IDF Diabetes Atlas, 5 th edition. Brussels, Belgium. Last accessed August 2013, available at: http://www.idf.org/diabetesatlas.
16. 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.

* EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome

† Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Subjects With Type 2 Diabetes Mellitus;