US FDA and EMA accept submission of BOSULIF for CML treatment


Applications seek to expand approved use of BOSULIF into first-line treatment based on positive results from Phase 3 head-to-head trial

US FDA and EMA accept submission of BOSULIF for CML treatment

Pfizer and Avillion announced a supplemental new drug application for BOSULIF has been accepted for filing and granted priority review by the US Food and Drug Administration (FDA).

If approved, the supplemental new drug application (sNDA) would expand the approved use of BOSULIF to include patients with newly diagnosed chronic phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).

BOSULIF (bosutinib) is currently indicated in the US for the treatment of adult patients with Ph+ CML with resistance or intolerance to prior therapy.

Priority review status accelerates FDA review time from 10 months to a goal of 6 months from the day of acceptance of filing and is given to drugs that may offer major advances in treatment or may provide a treatment for which no adequate therapy exists.

The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in December 2017.

In addition, the European Medicines Agency (EMA) has validated for review a Type II Variation application for use of BOSULIF in the same patient population.

In Europe, BOSULIF has conditional marketing authorisation for the treatment of adult patients with Ph+ CML previously treated with one or more tyrosine kinase inhibitors (TKIs) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

The submissions are based on results from BFORE (Bosutinib trial in First line chronic myelogenous leukemia treatment), a multi-centre, multinational, open-label Phase 3 study which showed BOSULIF 400 mg was associated with a significantly higher rate of patients achieving major molecular response (MMR) at 12 months (the primary endpoint) compared to the rate achieved in patients treated with imatinib.

Results from the trial were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in May 2017 and at the European Haematology Association (EHA) Meeting in June 2017.

The adverse events seen in the trial were consistent with the known safety profile for BOSULIF. The proposed dosing for the newly diagnosed patients is 400 mg daily, which is different from the currently approved dosing in patients who are resistant or intolerant to prior TKI therapy (500 mg daily).

Dr Mace Rothenberg, Chief Development Officer of Oncology at Pfizer Global Product Development, said: "As physicians gained experience with BOSULIF, they have come to appreciate its favourable risk-benefit profile in patients with Ph-positive CML who no longer responded to or could not tolerate prior TKI therapy.

"At the 400 mg dose, we believe that the BFORE study demonstrates a similarly favourable risk-benefit in previously untreated patients with Ph-positive CML. We look forward to working with the FDA in our efforts to expand the label for BOSULIF to include this important group of patients."

Dr Allison Jeynes-Ellis, CEO of Avillion, said: "These are important milestones for the CML community and for our partnership with Pfizer, which represent the commitment of both of our companies to work collaboratively toward our ultimate goal of improving the lives of patients."

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 and conducted the trial to generate the clinical data used to support these applications and other potential regulatory filings for marketing authorisation for BOSULIF as first-line treatment for patients with chronic phase Ph+ CML.

If approved for this indication, Avillion will be eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialise BOSULIF globally.

Pfizer is advancing a broad range of therapies that leverage select pathways and mechanisms of action to address acute and chronic leukemias, myeloproliferative disorders and lymphoma.

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