The CHMP will delay its decision on the future of pioglitazone-containing medicines until July.
Reviews are on-going into the results from several studies to assess the occurrence of bladder cancer, and to assess their impact on the balance of the benefits and risks of the medicines.
The Committee says at this stage there are still “numerous issues” that need to be resolved before it can make a final recommendation.
Pioglitazone-containing medicines include Actos, Glustin, Competact, Glubrava and Tandemact.
The link between bladder cancer in association with pioglitazone has been under review for more than a decade by the CHMP since it was first granted marketing authorisation.
The current review of pioglitazone-containing medicines was initiated in March at the request of the European Commission, following an increased number of spontaneous reports of bladder cancer.
Since then pharmacoepidemiological studies, non-clinical and clinical data and post-marketing reports are all being conducted by the EMA.
Takeda, the marketing authorisation holder, is also conducting a series of post-authorisation studies aimed at identifying incident malignancies associated with pioglitazone treatment in a cohort of diabetic patients.
Three interim studies by Takeda have not yet confirmed a clear association, but signal a potential increased risk in those with the longest exposure and highest cumulative dose.
The CHMP says that the accumulated evidence provided by additionally preclinical studies, epidemiological data and the PROactive trial (a placebo-controlled clinical trial) taken in its totality, represents a clinically relevant signal which requires further evaluation.
At the CHMP’s June meeting, the results of a retrospective cohort study carried out in France were discussed. The Committee considered that the study strengthened the signal of a small increased risk of bladder cancer. But it was also found that the study had several methodological limitations which limit the strength of evidence.
The Scientific Advisory Group on Diabetes/Endocrinology (SAG-D/E) has now been asked to discuss the place of pioglitazone-containing medicines for the treatment of diabetes and the clinical relevance of the available data on any cancer risk, and to identify risk-minimisation measures for patients in clinical practice.
Recommendations of the SAG-D/E will be analysed and discussed at the CHMP’s next meeting in July, where a final option on the benefits and risks of these medicines will be made.