What is Iclusig - ponatinib used for and what is it used for?
Iclusig is a cancer medicine that contains the active substance ponatinib . It is used to treat adult patients with the following types of leukemia (cancer of white blood cells):
- chronic myelogenous leukemia (CML) in its various phases: chronic, accelerated and blast;
- acute lymphoblastic leukemia (ALL) in patients with "Philadelphia positive chromosome" (Ph +). The Ph + expression means that some patient genes have reorganized themselves to form a special chromosome, called precisely "Philadelphia chromosome", which determines the development of leukemia. The Philadelphia chromosome is found in some patients with ALL and is present in most CML patients.
Iclusig is not used in patients who cannot tolerate or who do not respond to therapy with other anticancer medicines of the same class, ie dasatinib or (for patients with CML) nilotinib, and in whom subsequent treatment with imatinib (another anticancer medicine ) is not considered appropriate. It is also used in patients with a genetic mutation called the "T315I mutation", which makes them resistant to treatment with imatinib, dasatinib or nilotinib. Because the number of patients with CML and ALL is low, the diseases are considered "rare" and Iclusig was qualified as an "orphan medicine" (a medicine used in rare diseases) on 2 February 2010.
How is Iclusig - ponatinib used?
Iclusig can only be obtained with a prescription and treatment should be started by a doctor experienced in the diagnosis and treatment of patients with leukemia. Iclusig is available as tablets (15 mg and 45 mg). The recommended dose is 45 mg once a day. Treatment must be continued until the disease progresses or until the patient can no longer tolerate the medicine. Iclusig can lead to clots or blockages in the arteries and in the veins: doctors must take into account the cardiac condition and the circulation of the patients before starting the treatment and during the same. Patients must be treated appropriately if problems arise. If the patient complains of some side effects, it may be necessary to reduce the dose or stop the administration; if a blockage develops in an artery or vein it is necessary to stop therapy immediately. For more information, see the package leaflet.
How does Iclusig - ponatinib work?
Ponatinib, the active ingredient in Iclusig, belongs to a class of medicines called "tyrosine kinase inhibitors". These compounds act by inhibiting a class of enzymes known as tyrosine kinase. Ponatinib works by blocking a tyrosine kinase called Bcr-Abl. The enzyme is found in some receptors on the surface of leukemic cells, where it helps to stimulate cells to divide uncontrollably. By blocking Bcr-Abl, Iclusig helps control the growth and spread of leukemia cells.
What benefit has Iclusig - ponatinib shown during the studies?
Iclusig was examined in one main study involving 449 patients with CML or Ph + ALL who were intolerant or resistant to treatment with dasatinib or nilotinib, or who presented with a T315I mutation. During the study, Iclusig was not compared to another treatment. The response to treatment was evaluated by measuring the percentage of patients who had an "important haematological response" (when the number of white blood cells returns to normal or when there is no sign of leukemia) or a "major cytogenetic response" (when the percentage of white blood cells containing the Philadelphia chromosome falls below 35%). The results of the study showed that Iclusig therapy resulted in clinically relevant responses in all patient groups:
- among patients with chronic phase CML, approximately 54% (144 of 267) had an important cytogenetic response;
- among patients with accelerated phase CML, approximately 58% (48 of 83) had an important haematological response;
- among patients with CML in blast phase, about 31% (19 of 62) had an important haematological response;
- among patients with Ph + ALL in accelerated phase, about 41% (13 of 32) had an important haematological response.
What is the risk associated with Iclusig - ponatinib?
The most common side effects with Iclusig (which may affect more than 1 in 100 people) are pancreatitis (inflammation of the pancreas), abdominal pain (stomach ache), pyrexia (fever), anemia (low number of red blood cells in the blood), febrile neutropenia (low number of white blood cells associated with fever), reduced levels of platelets (components that promote blood clotting) and neutrophils (a type of white blood cells), myocardial infarction (heart attack), diarrhea, dyspnoea (difficulty of breathing), increased levels of lipase (an enzyme) and pancytopenia (low total number of blood cells). The most common side effects of any kind (which may affect more than 2 in 10 people) are decreased platelet levels, rash, dry skin and abdominal pain. For the full list of restrictions and side effects reported with Iclusig, see the package leaflet.
Why has Iclusig - ponatinib been approved?
The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Iclusig's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that Iclusig was effective in patients with CML or Ph + ALL for which limited treatment options were available. Regarding safety, the undesirable effects with Iclusig were largely similar to those of other tyrosine kinase inhibitors and mostly manageable with a dose reduction or a postponement of the same dose administration. The risk of problems (including heart attacks and strokes) resulting from blood clots or blockages in the arteries or veins can be reduced by checking and treating the concomitant conditions, such as high blood pressure and high cholesterol both before and during treatment .
What measures are being taken to ensure the safe and effective use of Iclusig - ponatinib?
A risk management plan has been developed to ensure that Iclusig is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Iclusig, including the appropriate precautions to be followed by healthcare professionals and patients.
More information on Iclusig - ponatinib
On 1 July 2013, the European Commission issued a marketing authorization for Iclusig, valid throughout the European Union. For more information on Iclusig therapy, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. Last update of this summary: 08-2014.
