ARIAD Pharmaceuticals, Inc., an emerging global oncology company, has submitted marketing authorization application (MAA) to the European Medicines Agency (EMA) for its investigational BCR-ABL inhibitor, ponatinib.
ARIAD is seeking marketing approval in the European Union of ponatinib in adult patients with resistant or intolerant chronic myeloid leukaemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukaemia (Ph+ ALL).
The Committee for Medicinal Products for Human Use (CHMP) has granted ARIAD’s request for accelerated assessment of the MAA.
“The accelerated assessment granted to our MAA further illustrates the major unmet medical need among patients with CML and Ph+ ALL who have become resistant or intolerant to prior tyrosine kinase inhibitor therapy,” stated Harvey J Berger, MD, chairman and chief executive officer of ARIAD. “As we establish our European headquarters in Lausanne, Switzerland and develop our commercial infrastructure in the region, our regulatory team will continue to work closely with the EMA as it reviews our data and the submission, potentially along an accelerated timeline.”
Results from the ongoing PACE trial of ponatinib reported in June at this year’s annual meeting of the American Society of Clinical Oncology, and included in the MAA, showed that 54 per cent of chronic-phase CML patients who were resistant or intolerant to prior tyrosine kinase inhibitor therapy in the trial, including 70 per cent of patients who have a T315I mutation, achieved a major cytogenetic response (MCyR) – the primary endpoint of the trial. Thirty per cent of these same patients achieved a major molecular response (MMR). MMR is the primary endpoint of ARIAD’s ongoing phase III EPIC trial comparing ponatinib to imatinib in newly diagnosed chronic-phase CML patients.
Internally discovered at ARIAD, ponatinib is an investigational BCR-ABL inhibitor that also selectively inhibits certain other tyrosine kinases in preclinical studies, including FLT3, RET, KIT, and the members of the FGFR and PDGFR families of kinases. A New Drug Application for ponatinib was submitted to the US Food and Drug Administration on July 30, 2012.
The primary target for ponatinib is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukaemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukaemia (Ph+ ALL). Ponatinib was designed using ARIAD’s computational and structure-based drug design platform to inhibit the activity of BCR-ABL with very high potency and broad specificity. Ponatinib targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment with existing tyrosine kinase inhibitors, including the T315I mutation for which no effective therapy currently exists.
CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase or blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukaemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. Because both of these diseases express the BCR-ABL protein, this would render them potentially susceptible to treatment with ponatinib.
ARIAD Pharmaceuticals, Inc. is an emerging global oncology company focused on the discovery, development and commercialization of medicines to transform the lives of cancer patients.