Products

Date: 2017-12-19

Type of information: Granting of a Market Authorisation in the US

Product name: Bosulif®

Compound: bosutinib

Therapeutic area: Cancer - Oncology

Action mechanism:

• kinase inhibitor. Bosulif® is intended for patients with chronic, accelerated or blast phase Philadelphia chromosome positive CML who are resistant to or who cannot tolerate other therapies, including imatinib. Bosulif® works by blocking the abnormal tyrosine kinase (Bcr-Abl kinase) that promotes the development of abnormal and unhealthy granulocytes.

Company: Pfizer (USA - NY)

Disease:

• Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML)
• patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML)

Latest news:

• • On December 19, 2017, Pfizer announced the FDA) approved a supplemental New Drug Application (sNDA) to expand the indication for Bosulif® (bosutinib) to include adult patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). The sNDA was reviewed and approved under the FDA’s Priority Review and accelerated approval programs based on molecular and cytogenetic response rates. Continued approval for this indication may be contingent upon verification and confirmation of clinical benefit in an ongoing long-term follow up trial. Bosulif® was first approved in September 2012 in the U.S. for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy.
• The approval was based on results from BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment) study. The study enrolled 536 patients at multiple sites in North America, Asia and Europe. Patients were randomized 1:1 to receive Bosulif®400 mg or imatinib 400 mg, a standard of care, for the duration of the study. The primary outcome was to show superiority of Bosulif® over imatinib at 12 months by comparing MMR, or the proportion of patients in each arm whose levels of the Bcr-Abl1 kinase have dropped below 0.1%. This randomized multicenter, multinational, open-label Phase 3 study showed Bosulif® 400 mg was associated with a significantly higher rate of patients achieving major molecular response (MMR) at 12 months (47.2%; 95% CI, 40.9-53.4) compared to the rate achieved in patients treated with imatinib 400 mg (36.9%; 95% CI, 30.8-43.0), a current standard of care (two-sided P=0.0200). Complete cytogenic response (CCyR) rate by 12 months was 77.2% (95% CI: 72.0, 82.5) for patients treated with Bosulif® compared to 66.4% (95% CI: 60.4, 72.4) for patients treated with imatinib (two-sided P=0.0075). The adverse events seen in the trial were consistent with the known safety profile for Bosulif®. The most common adverse reactions in newly diagnosed CML patients treated with Bosulif® (incidence ?20%) are diarrhea (70%), nausea (35%), thrombocytopenia (35%), rash (34%), increased alanine aminotransferase (ALT) (31%), abdominal pain (25%), and increased aspartate aminotransferase (AST) (23%).
• • On March 28, 2013, Pfizer has announced that the European Commission has granted conditional marketing authorization for Bosulif® (bosutinib) in the European Union for the treatment of adult patients with chronic phase, accelerated phase and blast phase  Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options. The decision was based on data from Study 200, a global, single-arm, open-label, multi-cohort, Phase 1/2 study of Bosulif® in more than 500 patients with Ph+ CML who had previously been treated with at least one tyrosine kinase inhibitor. The study included separate cohorts for patients with chronic, accelerated and blast phase disease. Data on 52 patients were considered as main evidence for the conditional marketing authorization, as these patients were identified as having an unmet medical need because other tyrosine kinase inhibitors were not considered appropriate treatment options for them due to disease resistance or the risk of severe side effects.
• • On January 17, 2013,  the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorisation for the medicinal product Bosulif® 100 mg and 500 mg film-coated tablets intended for the treatment of chronic myelogenous leukaemia. Bosulif® was designated as an orphan medicinal product on 4 August 2010. The approved indication is: “Bosulif® is indicated for the treatment of adult patients with chronic phase, accelerated phase , and blast phase Philadelphia chromosome positive chronic myelogenous leukaemia (Ph+ CML) previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.” It is proposed that therapy with Bosulif® be initiated by a physician experienced in the diagnosis and the treatment of patients with CML. A pharmacovigilance plan for Bosulif® will be implemented as part of the marketing authorisation.
• • On September 4, 2012, the FDA has approved Bosulif® (bosutinib) to treat chronic myelogenous leukemia (CML), a blood and bone marrow disease that usually affects older adults. An estimated 5,430 men and women will be diagnosed with CML in 2012. Most people with CML have a genetic mutation, called the Philadelphia chromosome, which causes the bone marrow to make an enzyme called tyrosine kinase. This enzyme triggers the development of too many abnormal and unhealthy white blood cells called granulocytes.
• The safety and effectiveness of Bosulif® was evaluated in a single clinical trial that enrolled 546 adult patients who had chronic, accelerated or blast phase CML. All patients had disease that progressed after treatment with imatinib or imatinib followed by dasatinib and/or nilotinib, or who could not tolerate the side effects of prior therapy. All patients in the trial were treated with Bosulif®.
• In patients with chronic phase CML, efficacy was determined by the number of patients who experienced a major cytogenetic response (MCyR) within the first 24 weeks of treatment. Results showed 34 percent of patients who had been previously treated with imatinib achieved MCyR after 24 weeks. Of the patients who achieved MCyR at any time, 52.8 percent had their response last at least 18 months. Among patients previously treated with imatinib followed by dasatinib and/or nilotinib, about 27 percent achieved MCyR within the first 24 weeks of treatment. Of those who achieved MCyR at any time, 51.4 percent had their MCyR last at least nine months.
• In patients with accelerated CML previously treated with at least imatinib, 33 percent had their blood counts that returned to normal range (complete hematologic response) and 55 percent achieved normal blood counts with no evidence of leukemia (overall hematologic response) within the first 48 weeks of treatment. Meanwhile, 15 percent and 28 percent of patients with blast phase CML achieved complete hematologic response and overall hematologic response, respectively.
• The most common side effects observed in those receiving Bosulif were diarrhea, nausea, a low level of platelets in the blood (thrombocytopenia), vomiting, abdominal pain, rash, low red blood cell count (anemia), fever and fatigue.
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Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2012-09-04

UE authorization: 2013-03-28

Favourable opinion UE: 2013-01-17

Favourable opinion USA:

Orphan status USA: 2009-02-24

Orphan status UE: 2010-08-04

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes