Avillion announces that the FDA today approved a supplemental sNDA for Pfizer’s BOSULIF (bosutinib).
Approval based on the successful BFORE Phase 3 study conducted by Avillion under a collaborative development agreement with Pfizer
London, UK, December 19, 2017 – Avillion, a drug development company focused on the co-development and financing of pharmaceutical candidates from proof-of-concept through to regulatory approval, announces that the U.S. Food and Drug Administration (FDA) today approved a supplemental New Drug Application (sNDA) for Pfizer’s BOSULIF® (bosutinib). The approved sNDA expands the indication for BOSULIF to include the treatment of adult patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).
The approval was based on positive results from the randomized, multinational BFORE Phase 3 study, which was conducted successfully by Avillion under an exclusive collaborative development agreement with Pfizer. The sNDA was reviewed and approved under the FDA’s Priority Review and accelerated approval program based on molecular and cytogenetic response rates demonstrated by BOSULIF. BOSULIF is also indicated 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.
Avillion provided funding and undertook the BFORE study to generate the clinical data used to support this application and other potential regulatory filings for marketing authorisation for BOSULIF as first-line treatment for patients with chronic phase Ph+ CML. Avillion is eligible to receive milestone payments from Pfizer based on this approval. Pfizer retains all rights to commercialize BOSULIF globally.
Prof. Tim H. Brümmendorf, Director of the Clinic for Oncology, Haematology and Stem Cell Transplantation at the Euregionales Comprehensive Cancer Center Aachen (ECCA), and European lead investigator on BFORE, added: “Molecular targeted therapy has substantially improved outcomes of patients with CML over that last two decades. Due to its efficacy and distinct tolerability profile, BOSULIF significantly expands our treatment options for newly diagnosed CML patients.”
Allison Jeynes-Ellis, MD, Chief Executive Officer of Avillion, said: “We are delighted with the approval today of BOSULIF by the US FDA. It not only adds an important treatment option for newly diagnosed Ph+ CML patients, but also represents a significant validation of our innovative business model and capabilities for the co-development and partnership of late-stage clinical candidates. Our model provides pharma partners with opportunities and capacity to advance additional late-stage clinical projects in parallel to their own development efforts. This achievement is testament to the expertise and hard work of the teams at Avillion and Pfizer, and we look forward to replicating this success in other partnerships.”
“Today’s approval is a testament to the strength of our partnership with Avillion and to the commitment of both of our companies to work together to improve lives for patients living with CML,” added Liz Barrett, Global President, Pfizer Oncology.
Efficacy and safety data support BOSULIF approval
The BOSULIF approval was based on results from BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment), a randomized multi-center, 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 (47.2%; 95% CI, 40.9-53.4) compared to the rate achieved in patients treated with imatinib 400mg (36.9%; 95% CI, 30.8-43.0), a current standard of care. Complete cytogenic response (CCyR) rate by 12 months was 77.2% for patients treated with BOSULIF compared to 66.4% for patients treated with imatinib (P<0.008), with time to CCyR shorter for patients treated with BOSULIF (HR 1.38; P≤0.001). The adverse events seen in the trial were consistent with the known safety profile for BOSULIF. The most common adverse events in newly diagnosed CML patients treated with BOSULIF (incidence ≥20%) are diarrhea, nausea, thrombocytopenia, increased alanine aminotransferase (ALT), rash, abdominal pain, and increased aspartate aminotransferase (AST). For more information, please see Important Safety Information for BOSULIF below.
About Chronic Myelogenous Leukemia (CML)
Chronic myelogenous leukemia (CML) is a rare blood cancer, which begins in the bone marrow, but often moves into the blood.1 Researchers estimate that by 2020, more than 412,000 people worldwide will be diagnosed with leukemia (all types)2. CML accounts for 10-15% of all incident leukemia cases.3 In the U.S., approximately 48,000 people are living with CML.1 Around 9,000 new CML cases were diagnosed in the U.S. in 2017.2
1American Cancer Society. What is Chronic Myeloid Leukemia? [Link] Accessed August 2017.
2GLOBOCAN Online Analysis/Prediction. [Link] Accessed August 2017.
3Hochhaus, A. Educational Session: Managing Chronic Myeloid Leukemia as a Chronic Disease. American Society of Hematology. 2011; 10: 1.
About BOSULIF® (bosutinib)
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 U.S., BOSULIF (bosutinib) is now indicated for the treatment of patients with newly-diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) and 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). A 400mg tablet was also recently approved by the FDA in addition to the previously approved 100mg and 500mg strengths. The recommended dose for newly diagnosed patients is 400 mg orally once daily with food. For patients who are resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy, the recommended dose is 500mg orally once daily with food.
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. The European Medicines Agency (EMA) has also validated for review a Type II Variation application for use of BOSULIF in the same patient population.
About the BFORE Study
BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment) is a multi-center, open-label Phase 3 study designed to assess the effectiveness and safety of BOSULIF® (bosutinib) as a first-line treatment for patients with chronic phase Ph+ CML. The study enrolled 536 patients at multiple sites in North America, Asia and Europe. Patients were randomized 1:1 to receive BOSULIF 400mg or imatinib, a standard of care, for the duration of the study. The primary outcome was to show superiority of bosutinib 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%.
