Takeda Pharmaceutical Co. Ltd. announced that the European Commission has granted Marketing Authorization (MA) for Vipidia (alogliptin), a dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of type 2 diabetes patients who are uncontrolled on existing therapies and for the fixed-dose combination (FDC) therapies Vipdomet (alogliptin with metformin) and Incresync (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.
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). Alogliptin is the first agent for the treatment of type 2 diabetes to be licensed with demonstrated CV safety outcomes data.
“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 and 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 Authorization 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 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 demonstrated that alogliptin 25 mg 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). Results also showed that when alogliptin was given in combination with metformin, significantly more patients achieve target HbA1c of ≤ 7 percent compared with an SU in combination with metformin.
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 25 mg 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. Previous trials indicated that alogliptin co-administered with either metformin or pioglitazone produced significant improvements in glycemic control compared with the respective monotherapies.
Common adverse events reported with alogliptin include upper respiratory tract infection, nasopharyngitis, headache, abdominal pain, gastroeosophageal reflux (GERD), pruritus and rash.
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. 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.
“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 Simon Heller, professor of Clinical Diabetes at the University of Sheffield, Sheffield, UK and EXAMINE trial investigator. “[This] 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 personalized 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).
Takeda received approval for alogliptin (Nesina) in 2010 and in fixed-dose combination with pioglitazone (Liovel) in 2011 in Japan. In the U.S., 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.
Date: September 24, 2013