Takeda announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicine's Agency (EMEA) has confirmed the positive risk-benefit balance for Actos (pioglitazone). After assessing all available data, the CHMP concluded that the benefits of pioglitazone in the treatment of type 2 diabetes continue to outweigh the risks. No changes to the prescribing information of pioglitazone were considered necessary.
Recently, the CHMP agreed that some information on a large cardiovascular outcome study (PRO active) could be included in section 5. The prescribing information now includes a statement on the cardiovascular safety of Actos which reads: "Although the study [PRO active] failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone". This makes Actos the only thiazolidinedione with information from a large cardiovascular outcome study in its prescribing information.
The CHMP also reviewed the concomitant use of pioglitazone and insulin and recommended not only the removal of the contraindication for use in combination with insulin but also to include combination therapy with insulin in type-2 diabetes mellitus patients with insufficient glycaemic control on insulin for whom metformin is inappropriate because of contraindications or intolerance.
This recommendation made Actos the only thiazolidinedione whose indications include use with insulin. Both the absence of long-term cardiovascular concerns as well as the indication to use Actos with insulin was upheld in the latest CHMP thiazolidinedione benefit-risk assessment.
Recently, the CHMP has also adopted a positive opinion for Competact (pioglitazone/metformin) and Tandemact (pioglitazone/glimepiride) to recommend the deletion of the contraindication for its use in combination with insulin.
Given the strength of the data, especially as demonstrated by the PRO active trial, Takeda remains confident in the pioglitazone safety profile regarding the risk of cardiovascular events. Takeda continuously looks at the safety and efficacy of pioglitazone with a particular emphasis on cardiovascular health, and has maintained a robust clinical trial program in the area. Takeda is committed to the analysis and communication of drug safety issues.
Pioglitazone was approved by the European Medicines Agency for the treatment of type-2 diabetes in October 2000. The original label was most recently extended in January 2007. In Europe, pioglitazone is indicated in the treatment of type 2 diabetes mellitus.
Pioglitazone is also indicated for combination with insulin in type 2 diabetes mellitus patients with insufficient glycaemic control on insulin for whom metformin is inappropriate because of contraindications or intolerance
Takeda also manufactures Competact, which combines two widely used diabetes treatments (metformin and pioglitazone) in a convenient single tablet, to be taken twice daily. Competact was first launched in Europe in October 2006.
Competact 15mg/850mg tablets contain 15mg pioglitazone as hydrochloride and 850mg of metformin hydrochloride. Indication: Treatment of type 2 diabetes mellitus patients, particularly overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone.
Tandemact 30mg/4mg tablets contain 30 mg pioglitazone as hydrochloride and 4 mg glimepiride. Indication: treatment of patients with type 2 diabetes mellitus who show intolerance to metformin or for whom metformin is contraindicated and who are already treated with a combination of pioglitazone end glimepiride.
PRO active was a prospective, randomised, placebo-controlled outcomes trial. The PRO-active study included 5,238 patients with type 2 diabetes and a history of macrovascular disease, who was force titrated up to 45 mg daily of either Actos or placebo. In this study, there was no difference in the number of macrovascular events between standard of care and Actos, and standard of care alone. Although the study failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone.
The Actos Summary of Product Characteristics was recently revised by the EMEA to include this reassuring cardiovascular safety data. Actos is the only thiazolidinedione (TZD) with safety data from a cardiovascular outcomes trial in its label.
Takeda Pharmaceutical Company Limited, located in Osaka, Japan, 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.