Pfizer Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted positive opinions recommending that two Pfizer haematology medicines be granted marketing authorizations in the European Union (EU).

Mylotarg (gemtuzumab ozogamicin) in combination with daunorubicin and cytarabine has been granted a positive opinion for the treatment of patients age 15 years and above with previously untreated, de novo, CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL).

Bosulif (bosutinib) has been granted a positive opinion for the treatment of adults with newly diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukaemia (Ph+ CML). The CHMP’s opinions for both medicines will now be reviewed separately by the European Commission (EC).

“There is an urgent need to improve outcomes for leukaemia patients in Europe,” said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. “If approved, the addition of Mylotarg to standard chemotherapy will provide an important new treatment option for patients with acute myeloid leukaemia who would typically be treated with chemotherapy alone. Additionally, the potential expansion of the approved use of Bosulif to include first-line therapy expands the treatment options for adult patients with newly diagnosed chronic myelogenous leukaemia.”

The Marketing Authorization Application (MAA) for Mylotarg was based on data from an investigator-led, Phase 3, randomized, open-label study (ALFA-0701) in previously untreated, de novo patients.

Bosulif currently has conditional marketing authorization in Europe related to the initial marketing authorization. The Type II Variation application for Bosulif for adults with newly diagnosed chronic phase Ph+ CML was based on results from BFORE (Bosutinib trial in First line chrOnic myelogenous leukaemia tREatment), a randomized multicenter, multinational, open-label, phase 3, head-to-head study of Bosulif 400 mg versus imatinib 400 mg, a current standard of care.

Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial. Under the terms of the agreement, Avillion provided funding for the trial to generate the clinical data used to support this application and other potential regulatory filings for marketing authorization for Bosulif as first-line treatment for patients with chronic phase Ph+ CML. Pfizer retains all rights to commercialize Bosulif globally.

Mylotarg is an antibody-drug conjugate (ADC) composed of the cytotoxic agent calicheamicin, attached to a monoclonal antibody (mAB) targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90 per cent of AML patients. When Mylotarg binds to the CD33 antigen on the cell surface it is absorbed into the cell and calicheamicin is released causing cell death.

Mylotarg was approved by the US Food and Drug Administration in September 2017 for adults with newly diagnosed CD33-positive AML, and adults and children 2 years and older with relapsed or refractory CD33-positive AML. Mylotarg was originally approved in 2000 at a higher dose under the FDA’s accelerated approval program for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years or older and who were not considered candidates for other cytotoxic chemotherapy. In 2010, Pfizer voluntarily withdrew Mylotarg in the US after a confirmatory trial failed to show clinical benefit and there was a higher rate of fatal toxicity compared to chemotherapy. Mylotarg has been available to individual patients through Pfizer’s compassionate use programmes.

In addition, Mylotarg is commercially available in Japan where it has been approved since 2005 for the treatment of patients with relapsed or refractory CD33-positive AML who are not considered candidates for other cytotoxic chemotherapy.

Mylotarg originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development and commercialization activities for this molecule.

Pfizer also collaborated with SFJ Pharmaceuticals Group on the registrational programme for Mylotarg.

Bosulif (bosutinib) is an oral, once-daily, tyrosine kinase inhibitor (TKI), which inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases. In the US, Bosulif (bosutinib) is indicated for the treatment of adult patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukaemia (Ph+ CML). Continued approval for this indication may be contingent upon verification and confirmation of clinical benefit in an ongoing long-term follow up trial. Bosulif is also indicated in the US for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy (first approved in September 2012).

In Europe, Bosulif was granted conditional marketing authorization in March 2013 for the treatment of adult patients with Ph+ CML previously treated with one or more TKIs and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.