PRAC recommendations to be considered by CHMP for final opinion

The EMA’s Pharmacovigilance Risk Assessment committee (PRAC) has completed a review of the benefits and risks of Iclusig (ponatinib), a medicine used for the treatment of leukaemia (cancer of the white blood cells). The aim of this review was to examine the risk of blood clots or blockage of the arteries or veins and to assess whether further measures were needed to minimise this risk.

Iclusig is authorised for use in patients with chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL) who cannot take or tolerate several other medicines of the same class (known as ‘tyrosine-kinase inhibitors’). The PRACconsidered that the benefits of Iclusig continue to outweigh its risks; however, the Committee recommended that the product information for patients and healthcare professionals should be updated with strengthened warnings, particularly about the risk of blood clots and blockages in the arteries.

The PRAC assessed the available data on the nature, frequency and severity of blood clots or blockage of the arteries or veins. Although the Committee noted that this risk is likely to be dose-related, there are insufficient data to formally recommend the use of lower doses of Iclusig, and there is a risk that lower doses might not be as effective in all patients and in long-term treatment. The PRAC therefore considered that the recommended starting dose of Iclusig should remain 45 mg once a day. However, updates to the product information are recommended to provide healthcare professionals with the latest evidence, in case they wish to consider reducing the dose in patients with ‘chronic phase’ CML who are responding well to treatment, and who might be at particular risk of blood vessel blockage. In addition, healthcare professionals should stop Iclusig if there has been no response after three months of treatment, and monitor patients for high blood pressure or signs of heart problems.

A new study on the safety and benefits of Iclusig is planned to help clarify if lower doses of the medicine carry a lower risk of blood clots or blockages of the blood vessels while still having a beneficial effect in patients with chronic phase CML.

The PRAC recommendation will now be forwarded to the Committee for Medicinal Products for Human Use (CHMP), which will adopt the EMA’s final opinion.


Posted on the EMA website on 10 October 2014