The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has made a number of recommendations to help minimise the risk of blood clots obstructing arteries or veins in patients taking the leukaemia medicine Iclusig.

The CHMP recommends that Iclusig should not be used in patients who have had a heart attack or stroke in the past, unless the potential benefits to them outweigh the risks. In addition, the cardiovascular risks of all patients should be assessed and measures should be taken to reduce risks before starting and during treatment with Iclusig. Patients who have high blood pressure should have their blood pressure controlled, and treatment with Iclusig should be stopped immediately in any patient with signs of blood clots obstructing arteries or veins.

The CHMP’s recommendations follow a review of updated clinical trial data indicating that blood clots were occurring at a higher rate than was observed at the time of the medicine’s initial authorisation. Conditions related to blood clots, such as heart attacks and strokes, were already considered to be possible side effects of Iclusig and were listed in the EU product information.

Since the medicine’s initial approval in July 2013, its use has been limited to patients who could not be treated with other medicines of the same class, for example, because patients were intolerant to the other medicines or their disease was resistant to them.

The CHMP recommendations are broadly in line with previous advice of the Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) and an opinion will be sent to the European Commission for an update of the EU product information.

The Agency now plans to conduct a further in-depth review of relevant data on the benefits and risks of Iclusig and will make recommendations on whether there should be further changes to how the medicine is used.

The recommendations are based on a review of data from clinical studies, including two ongoing studies (a phase I dose-finding study and a pivotal phase II study), which showed a higher incidence of arterial and venous thrombotic events in patients treated with Iclusig than was observed at the time of marketing authorisation. In the phase I study, preliminary analysis of follow-up data from September 2013 showed a rate of serious occlusive vascular events of 22 per cent (18 out of 81 patients) while in a preliminary analysis of data from the phase II study the rate was 13.8 per cent (62 out of 449 patients). Median treatment duration was 2.7 years in the phase I study and 1.3 years in the phase II study.

In addition, in a recently discontinued phase III study that compared Iclusig with imatinib with a median treatment duration of three months, there was a higher number of occlusive vascular events reported in the Iclusig arm, although the data from this study are still preliminary.

The reported events from the studies include cardiovascular, cerebrovascular, peripheral vascular and venous thrombotic events. These events were seen in patients with and without risk factors but were seen more frequently in older patients and patients with a history of ischaemia (such as heart attacks) and strokes, high blood pressure, diabetes or blood fat disorders.