EMA recommends revised labeling and guidance for pioglitazone-containing products

Takeda Pharmaceutical Company Limited (“Takeda”) announced today that the European Medicines Agency (EMA) has recommended changes to the label of pioglitazone-containing medicines. Following a review under Article 20 of Regulation (EC) No. 726/2004, the Agency’s Committee for Medicinal Products for Human Use (CHMP) confirmed that pioglitazone-containing medicines remain a valid treatment option for appropriate patients with type 2 diabetes. While a small increased risk of bladder cancer has been identified in patients taking these medicines, the CHMP concluded that this risk could be reduced by including new contraindications and warnings in the product labels regarding appropriate patient selection and exclusion, and periodic review of the efficacy and safety of the patient’s treatment.

Today’s EMA recommendation is independent from the actions taken by regulatory agencies in other markets. Takeda is dedicated to working closely with these regulatory agencies on appropriate next steps within each country.

The CHMP is responsible for preparing the EMA’s opinions on all questions concerning medicinal products for human use. The EMA Opinion will be forwarded to the European Commission for a final decision.

The CHMP initiated the European review of pioglitazone-containing medicines in March 2011 to investigate the signal of a possible increased risk of bladder cancer with pioglitazone use. As part of the process, the CHMP reviewed all available data on the occurrence of bladder cancer, including results of preclinical studies, clinical studies, epidemiological studies and spontaneous reports, to assess the balance of benefits and risks of these medicines. The Committee also considered the advice from its Scientific Advisory Group (SAG) on Diabetes/Endocrinology.

If the EMA’s opinion is adopted by the European Commission, Takeda will work with the EMA to implement the decision across Member States, and will update physician and patient information to reflect these changes. The company is dedicated to ensuring that pioglitazone-containing medicines are prescribed and monitored in accordance with the most current scientific analysis.

Takeda is confident in the therapeutic benefits of pioglitazone and its importance as a treatment for type 2 diabetes, and remains committed to pioglitazone and pioglitazone-containing medications, and to the millions of people living with type 2 diabetes. Patients currently on pioglitazone should have their treatments evaluated by their physician at their next scheduled appointment. Patients with any questions should speak to their physician. Takeda recommends that all patients taking pioglitazone-containing medications consult their health care provider before making any change to their type 2 diabetes regimen. Takeda has consistently emphasized the importance of physician education and patient safety in communications involving pioglitazone, and has prioritized communicating the appropriate use of pioglitazone in patients with type 2 diabetes.

“Takeda is committed to patient safety, and as a company we continuously monitor the safety and tolerability of all of our products. Our ongoing commitment to patients with type 2 diabetes means that we will continue to work with the EMA and other individual regulatory bodies to share and review all available data,” said Robert Spanheimer, M.D., Vice President, Medical and Scientific Affairs at Takeda.

As part of Takeda’s commitment to ongoing clinical research to understand and investigate potential safety concerns, working with appropriate regulatory agencies, it is currently supporting a ten-year epidemiological study, initiated in 2002 by the University of Pennsylvania (U. of Penn.) and Kaiser Permanente Diabetes Registry, Northern California (KPNC). The primary endpoint of an interim analysis, published in Diabetes Care April 2011, and reported to regulatory agencies on an ongoing basis, indicated that treatment with pioglitazone was not associated with a statistically significant increase in the incidence of bladder cancer. A secondary endpoint demonstrated that patients taking pioglitazone for more than 24 months showed a weak increased risk for bladder cancer. Takeda is committed to supporting this study through its conclusion at the end of 2012 and will report on the final results upon completion. Takeda is also supporting a long-term, observational study (EC 455 PROactive extension trial), which is expected to be completed by 2015. Further Takeda will initiate a pan-European epidemiologic study to further investigate these questions in Europe.