EMA Reviews PI3K Inhibitor Idelalisib

Review follows concerns over serious adverse events in ongoing clinical trials

The European Medicines Agency (EMA) has, at the request of the European Commission, started a review of idelalisib (Zydelig), which is authorised in the EU in combination with rituximab for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or as first line treatment in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy; it is also indicated as monotherapy for the treatment of adult patients with follicular lymphoma that is refractory to two prior lines of treatment.

The review has been started because an increased rate of serious adverse events including deaths, mostly due to infections, was seen in three clinical trials investigating the medicine in combination with other cancer medicines. The clinical trials involved patients with CLL and indolent non-Hodgkin lymphoma. However, the study in CLL investigated combinations of medicines that are currently not approved and the studies in non-Hodgkin lymphoma included patients with disease characteristics different from those covered by the currently approved indications.

Investigators of all clinical trials involving idelalisib are currently being informed of the actions to be taken in relation to the conduct of ongoing studies.

EMA will now review the data from these studies to assess whether the findings have any consequences for the authorised uses of idelalisib. In the meantime, patients starting or on treatment with idelalisib should be carefully monitored for signs of infections. If idelalisib is well tolerated, treatment should not be stopped.

EMA is considering whether any other immediate measures are necessary while the review is ongoing. The Agency will communicate further and keep doctors and patients informed as appropriate.

Patients who have any questions about their treatment should contact their doctor.

The review of idelalisib has been initiated at the request of the European Commission, under Article 20 of Directive 2001/83/EC.

The review is being carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which will make a set of recommendations. The PRAC recommendations will then be forwarded to the Committee for Medicinal Products for Human Use, responsible for questions concerning medicines for human use, which will adopt a final opinion.

The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all EU Member States.