Takeda Receives Positive CHMP Opinions for Label Updates to Vipidia™ (alogliptin) and Fixed-Dose Combinations Vipdomet™ (alogliptin and metformin) and Incresync™ (alogliptin and pioglitazone)

ZURICH, July 29, 2014 /PRNewswire/ -- Takeda Pharmaceuticals International GmbH ("Takeda") today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued positive opinions for updates to the Summary of Product Characteristics (SmPC) for Vipidia™ (alogliptin) and the fixed-dose combination (FDC) therapies Vipdomet™ (alogliptin and metformin) and Incresync™ (alogliptin and pioglitazone). If the recommendation is formally adopted by the European Commission alogliptin for the treatment of Type 2 diabetes would include demonstrated cardiovascular (CV) safety outcomes data in its labeling. Type 2 diabetes is the most common form of diabetes, accounting for 85-95 percent of all cases and affecting 382 million people worldwide.¹

The CHMP recommendation for each of these therapies includes updated findings from two clinical studies. Proposed changes to the SmPC for Vipidia, Vipdomet, and Incresync include additional information from the CV safety outcomes trial EXAMINE(EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome). Additionally, the proposed changes for Vipidia and Vipdomet also include updated findings from the ENDURE (Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Subjects With Type 2 Diabetes Mellitus) clinical study.^2,3,4,5 EXAMINE was conducted with 5,380 Type 2 diabetes patients, with recent acute coronary syndrome (ACS) and high underlying CV risk. EXAMINE evaluated the effect of treatment with alogliptin in addition to standard of care, versus placebo in addition to standard of care, on major adverse CV events (MACE).³ ENDURE was a three-arm, multi-center, randomized, double-blind, active-controlled study evaluating the durability of the safety and efficacy of once-daily alogliptin compared to glipizide, each in combination with metformin.⁴

"We're encouraged by the positive opinions for Vipidia, Vipdomet and Incresync as cardiovascular disease is the leading cause of morbidity and mortality in patients with Type 2 diabetes," said Elisabeth Genestin, MD, cardiometabolic medical affairs director, Europe & Canada, Takeda. "Having a robust data set demonstrating that alogliptin does not increase the risk of cardiovascular outcomes is important for the healthcare professionals who are treating people with Type 2 diabetes."

The most substantive change proposals include:

• An update to the Clinical Safety section:
  • Findings from EXAMINE demonstrated that use of alogliptin did not increase the risk of having a MACE compared to placebo [Hazard Ratio: 0.96; 1-sided 99% Confidence Interval: 0-1.16]. In the alogliptin group, 11.3% of patients experienced a MACE compared to 11.8% of patients in the placebo group.³ This further confirms results from a previously conducted pooled analysis of the data from 13 studies, where the overall incidences of CV death, non-fatal myocardial infarction and non-fatal stroke were comparable in patients treated with 25 mg alogliptin, active control or placebo.^3,4,5 In addition, in this prospective randomized controlled CV outcomes study, investigator reported events of hypoglycaemia were similar in patients receiving placebo (6.5%) and patients receiving alogliptin (6.7%) both in addition to standard of care.^3,4,5
• An update to the Clinical Efficacy section:
  • Results from ENDURE demonstrated that the addition of 25 mg alogliptin once daily to metformin hydrochloride therapy for glycemic control resulted in improvements from baseline in HbA1c at Week 52 that were sustained at Week 104.^3,4,5 At Week 52, the HbA1c reduction by alogliptin plus metformin was similar to that produced by glipizide plus metformin. At week 104 the HbA1c reduction by alogliptin plus metformin was greater than that produced by glipizide plus metformin.

The CHMP/EMA opinions for Vipidia, Vipdomet, and Incresync will now be sent to the European Commission to update the respective product Commission Decisions.² The European Commission first granted Marketing Authorization for Vipidia, Vipdomet, and Incresync in September 2013.

About Vipidia (alogliptin)

• Alogliptin is indicated for the treatment of Type 2 diabetes in adults aged 18 years and older to improve glycemic control in combination with other glucose lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycemic control³
• The usual recommended daily dose is 25 mg once daily (OD), with dose flexibility for all stages of renal impairment (no dose adjustment for mild renal impairment, 12.5 mg OD for moderate renal impairment, 6.25 mg OD for severe renal impairment or ESRD) ³
• Dipeptidyl peptidase-4 inhibitors (DPP-4i) address insulin deficiency by slowing the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide).³ As a result, an increased amount of active incretins enables the pancreas to secrete insulin in a glucose-dependent manner, thereby assisting in the management of blood glucose levels

About Vipdomet (alogliptin and metformin) fixed dose combination

Alogliptin and metformin is a FDC therapy for the treatment of Type 2 diabetes, which combines 12.5 mg alogliptin and 1000 mg metformin in a single tablet, taken twice daily.⁴ Vipdomet is indicated in the treatment of adult patients aged 18 years and older with Type 2 diabetes mellitus:

• as an adjunct to diet and exercise to improve glycemic control in adult patients, inadequately controlled on their maximal tolerated dose of metformin alone, or those already being treated with the combination of alogliptin and metformin⁴
• in combination with pioglitazone (i.e. triple combination therapy) as an adjunct to diet and exercise in adult patients inadequately controlled on their maximal tolerated dose of metformin and pioglitazone⁴
• in combination with insulin (i.e. triple combination therapy) as an adjunct to diet and exercise to improve glycemic control in patients when insulin at a stable dose and metformin alone do not provide adequate glycemic control⁴

About Incresync (alogliptin and pioglitazone) fixed dose combination

Alogliptin and pioglitazone is a FDC therapy for the treatment of Type 2 diabetes, which combines 25 mg alogliptin and 45 mg pioglitazone in a single tablet, taken once daily.⁵ Incresync is indicated as a second or third line treatment in adult patients aged 18 years and older with Type 2 diabetes mellitus:

• as an adjunct to diet and exercise to improve glycemic control in adult patients (particularly overweight patients) inadequately controlled on pioglitazone alone, and for whom metformin is inappropriate due to contraindications or intolerance⁵
• in combination with metformin (i.e. triple combination therapy) as an adjunct to diet and exercise to improve glycemic control in adult patients (particularly overweight patients) inadequately controlled on their maximal tolerated dose of metformin and pioglitazone⁵
  

About Type 2 diabetes

• In 2013, 382 million people worldwide were living with Type 2 diabetes. By 2035 this number is expected to rise to 592 million¹
• In 2013, the number of people with diabetes in Europe was estimated to be 56 million⁶
• The number of Type 2 diabetes patients is increasing in every country¹
• In 2013, one in 10 deaths in adults in Europe was attributed to diabetes, representing over 600,000 people¹
• Estimates indicate that more than EUR 108 billion* was spent on healthcare due to diabetes in the European region in 2013, accounting for over one-quarter of global healthcare expenditures due to diabetes¹
• Because of the increasingly complex nature of this disease, all patients require treatment to be individualized to their needs.⁷ Each patient responds differently to medications, and healthcare providers often must combine multiple treatment options to help patients manage their disease.

*Based on conversion of USD 147 billion,¹ where 1 EUR = 1.36035 USD as of 10 July 2014

About Takeda Pharmaceuticals International GmbH

Headquartered in Zurich as a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Osaka, Japan, the Company has a commercial presence covering more than 70 countries, with particular strength in Asia, North America, Europe and fast-growing emerging markets including Latin America, Russia-CIS and China. Areas of focus include cardiovascular and metabolic, oncology, respiratory and immunology, central nervous system, general medicine, and vaccines.

Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine. Through the integration of Millennium Pharmaceuticals and Nycomed, Takeda has been transforming itself, broadening its therapeutic expertise and geographic outreach.

Additional information about Takeda is available through its corporate website, www.Takeda.com.

About Takeda's Diabetes Business

Takeda's heritage in diabetes globally includes significant contributions towards scientific discovery and exchange, starting with the discovery of the thiazolidinedione (TZD) pioglitazone, the more recent developments of alogliptin and the fixed-dose combinations (FDC) alogliptin and pioglitazone, and alogliptin and metformin HCl. The company's strong, diverse diabetes portfolio and available medications mark important milestones in Takeda's ongoing commitment to advancing patient care and helping to meet the individual needs of this growing patient population.

References

¹ International Diabetes Federation. IDF Atlas, sixth edition. Last accessed July 10, 2014. Available at: http://www.idf.org/diabetesatlas.

² European Medicines Agency. Available at: http://www.ema.europa.eu/ema/.

³ Vipidia Summary of Product Characteristics. Last accessed July 10, 2014. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002182/WC500152271.pdf.

⁴ Vipdomet Summary of Product Characteristics. Last accessed July 10, 2014, available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002654/WC500152141.pdf.

⁵ Incresync Summary of Product Characteristics. Last accessed July 10, 2014, available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002178/WC500152197.pdf.

⁶ International Diabetes Federation. Diabetes: Facts and figures. Last accessed July 10, 2014. Available at: http://www.idf.org/worlddiabetesday/toolkit/gp/facts-figures.

⁷ Inzucchi SE, Bergenstal RM et al. Management of Hyperglycaemia in Type 2 Diabetes: A Patient-Centred Approach. Diabetes Care. 2012:35: (6):1364-1379.