Bosulif

Bosulif is available as tablets (100, 400 and 500 mg). It can only be obtained with a prescription and treatment should be started by a doctor who is experienced in the diagnosis and treatment of CML. The recommended dose is 400 mg once a day for newly diagnosed patients, and 500 mg once a day for patients who have already been treated with other medicines. The doctor may increase the dose up to 600 mg once a day or reduce it or interrupt treatment according to how the medicine is working and the side effects the patient has.

For more information about using Bosulif, see the package leaflet or contact a doctor or pharmacist.

The active substance in Bosulif, bosutinib, is a tyrosine kinase inhibitor. It blocks the action of enzymes known as Src and Bcr-Abl tyrosine kinases found on leukaemia cells where they are involved in stimulating the cells to divide uncontrollably. By blocking their action, Bosulif helps to control cell division, thereby controlling the growth and spread of the leukaemia cells in CML.

Studies have shown that Bosulif is effective at reducing the proportion of white blood cells with the Philadelphia chromosome. Bosulif was investigated in one main study involving 570 patients with Ph+ CML who had previously been treated with at least one tyrosine kinase inhibitor. Bosulif was not compared with another treatment. Of these, 52 patients were considered to have an unmet medical need, because disease resistance or the risk of severe side effects made other tyrosine kinase inhibitors unsuitable. Among these patients, 36 had chronic phase CML and 16 had either accelerated or blast phase CML.

The main measure of effectiveness was the number of patients who had at least a ‘major cytogenetic response’ (where the proportion of white blood cells with the Philadelphia chromosome fell below 35%) after six months of Bosulif treatment. Effectiveness was also measured in other ways including ‘haematological response’ (a return to normal of the number of white cells in the blood). Bosulif treatment was effective in patients with an unmet medical need: 18 out of 36 patients with chronic phase CML had a ‘major cytogenetic response’, while 7 out of the 16 patients with advanced (accelerated or blast phase) CML also had a sufficient response based on other measurements.

A second study in 536 newly diagnosed CML patients in the ‘chronic phase’ compared Bosulif with imatinib. The main measure of effectiveness was the number of patients who had a ‘major molecular response’ (where the amount in the bone marrow of BCR-ABL, the protein produced by the Philadelphia chromosome, is greatly lowered). After one year of treatment, 47% (116 out of 246) of patients treated with Bosulif had a major molecular response, compared with 37% (89 out of 241) of patients treated with imatinib.

The most common side effects with Bosulif (which may affect more than 1 in 5 people) are diarrhoea, nausea (feeling sick), thrombocytopenia (low blood platelet counts), abdominal pain (belly ache), vomiting, rash, anaemia (low red blood cell counts), tiredness, fever and increased levels of liver enzymes. The most serious side effects (which may affect more than 1 in 20 people) include thrombocytopenia, anaemia, diarrhoea, rash, neutropenia (low levels of neutrophils, a type of white blood cell) and blood tests suggesting damage to the liver and pancreas. For the full list of all side effects reported with Bosulif, see the package leaflet.

Bosulif must not be used in patients with reduced liver function. For the full list of restrictions, see the package leaflet.

Bosulif has been shown to improve the condition of patients with CML, including by reducing the number of cancer cells with the Philadelphia chromosome and returning white blood cell levels to normal. The side effects of the medicine are considered to be manageable.

The European Medicines Agency therefore decided that the benefits of Bosulif are greater than in its risks and recommended that it can be authorised for use in the EU.

Bosulif has been given ‘conditional authorisation’. This means that there is more evidence to come about the medicine, which the company is required to provide. Every year, the Agency will review any new information that becomes available and this summary will be updated as necessary.

Since Bosulif has been granted a conditional approval, the company that markets Bosulif will carry out and submit the results of a larger study with Bosulif in patients with Ph+ CML previously treated with one or more tyrosine kinase inhibitors and for whom dasatinib, imatinib and nilotinib are not considered appropriate treatment options.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Bosulif have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Bosulif are continuously monitored. Side effects reported with Bosulif are carefully evaluated and any necessary action taken to protect patients.

A is available.

Bosulif received a marketing authorisation valid throughout the EU on 27 March 2013.