Bosulif

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.

Bosulif received a conditional marketing authorisation valid throughout the EU on 27 March 2013. This was switched to a full marketing authorisation on 7 April 2022.

Bosulif is available as tablets and capsules to be taken by mouth once a day. Treatment can continue as long as the patient benefits from it and side effects are acceptable.

Bosulif 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.

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 (proteins) 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, bosutinib 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 or placebo. Of these, 52 patients were considered to have an unmet medical need, because disease resistance or the risk of severe side effects made treatment with 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 by measuring the 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.

Results from an extension of this study, during which patients who benefited from Bosulif were followed up for at least 10 years, confirmed that the effect of the medicine was maintained long term.

An additional study involved 163 patients with chronic or advanced Ph+ CML for whom previous treatment with at least one tyrosine kinase inhibitor did not work, or who could not take these medicines. The study showed that among the 156 patients with chronic Ph+ CML treated with at least one tyrosine kinase inhibitor, 72% had a major cytogenetic response. Among the 7 patients with advanced CML, 75% had a haematological response after one year of treatment.

A third 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.

An additional study was carried out in children and adolescents with chronic phase Ph+ CML; Bosulif was not compared with another treatment or placebo in this study. About 87% (26 out of 30) of newly diagnosed patients had a major cytogenetic response; 86% (24 out of 28) of patients who had been treated with at least one tyrosine kinase inhibitor before had a major cytogenetic response.

For the full list of side effects and restrictions with Bosulif, see the package leaflet

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 (belly) pain, vomiting, rash, anaemia (low red blood cell counts), tiredness, fever, increased levels of liver enzymes and headache. Side effects in children are similar to those in adults; children may also have decreased appetite.

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 increased levels of certain enzymes  suggesting damage to the liver and the pancreas.

Bosulif must not be used in patients with reduced liver function.

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 beneficial effects seen in children older than 6 years of age are comparable to those seen in adults. The side effects of the medicine are considered manageable.

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

Bosulif was originally given ‘conditional authorisation’. The authorisation was then switched to standard authorisation as the company has provided additional data requested by the Agency.