Iclusig (ponatinib): Withdrawal of EMA application for the treatment of adults newly diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL).
On 11 August 2023 Incyte Biosciences Distribution B.V. withdrew its application for the use of Iclusig in the treatment of adults newly diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL).
Based on the review of the information and the company’s response to the Agency’s questions, at the time of the withdrawal, the Agency’s provisional opinion was that Iclusig could not have been authorised for the proposed use based on the data submitted.
In particular, the Agency considered that although Iclusig was shown to have activity against the cancer in the study investigating its use in combination with chemotherapy, it was not possible to quantify the medicine’s benefits and risks. The lack of a comparator, together with the small size of the study, meant it was not possible to establish the relevance of the study results for the target patient population. In addition, the CHMP considered that more information was needed to establish the benefits of Iclusig when used with either high-intensity or reduced-intensity chemotherapy.
The Agency also had concerns about the second study investigating the use of Iclusig with corticosteroids in patients who could not receive chemotherapy and a stem cell transplant, which was of even smaller size and also lacked a comparator.
Furthermore, the numerous changes made to the study protocols and some incorrect information included in the dossier submitted to EMA required requesting an inspection to verify adherence of the studies to good clinical practice guidelines.
Therefore, at the time of the withdrawal, the Agency’s opinion was that the company had not fully addressed its concerns and the benefit and risks of Iclusig in the treatment of patients newly diagnosed with Ph+ ALL, in combination with chemotherapy or corticosteroids, could not be established.
In its letter notifying the Agency of the withdrawal of application, the company stated that it was not in a position to satisfactorily address the second round of questions raised by EMA’s human medicines committee, the CHMP.
There are no consequences on the use of Iclusig in its authorised uses. Iclusig is a cancer medicine approved for the treatment of adults with the following types of leukaemia (cancer of the white blood cells):
- chronic myeloid leukaemia (CML) in its different stages known as chronic, accelerated and blast phases;
- acute lymphoblastic leukaemia (ALL) in patients who are Philadelphia chromosome-positive (Ph+). Ph+ means that some of the patient’s genes have rearranged themselves to form a special chromosome, called the Philadelphia chromosome, that leads to the development of leukaemia. The Philadelphia-chromosome is found in some ALL patients and is present in most patients with CML.
Iclusig is approved for the treatment of patients who cannot tolerate or do not respond to dasatinib (patients with CML or ALL) or nilotinib (patients with CML), which are other cancer medicines of the same class, and for whom subsequent treatment with imatinib (a third such medicine) is not considered appropriate. It is also approved for the use in patients who have a genetic mutation known as T315I, which makes them resistant to treatment with imatinib, dasatinib or nilotinib.
Iclusig has been authorised in the EU since July 2013. It contains the active substance ponatinib and is available as tablets.