ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced updated clinical data from the pivotal PACE trial of its investigational pan-BCR-ABL inhibitor, ponatinib, in patients with chronic myeloid leukaemia (CML) or Philadelphia-positive acute lymphoblastic leukaemia (Ph+ ALL), who are resistant or intolerant to dasatinib or nilotinib or who have the T315I mutation. These data show that 54 percent of chronic-phase CML patients in the trial, including 70 percent of patients who have a T315I mutation, achieved a major cytogenetic response.
The PACE trial data were featured on Sunday at 8:30 a.m. (CET) in an oral presentation at the 2012 European Hematology Association (EHA) annual congress taking place in Amsterdam, The Netherlands. ARIAD expects to file for regulatory approval of ponatinib in the EU and in the U.S. in the third quarter of 2012 based on these clinical data.
"The pivotal PACE trial data show robust anti-leukaemic activity of ponatinib in patients with CML at all stages, who are resistant or intolerant to dasatinib or nilotinib, or who have the T315I mutation, a rare form of CML which has no available treatment options," said Jane F. Apperley, professor and chair, Department of Haematology at the Imperial College, and the chief of service, Clinical Haematology, at the Imperial College Healthcare NHS Trust, London, England. "Clinical responses to ponatinib were observed in patients regardless of their mutation status or disease stage, and the responses appear to be durable, with 93 percent of chronic-phase CML patients projected to remain in major cytogenetic response at one year. This clearly highlights the potency of ponatinib."
CML is a cancer of the white blood cells that is diagnosed in approximately 7,000 patients each year in Europe. CML is a type of leukaemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. The genetic hallmark of CML is the Philadelphia chromosome, an abnormality resulting in a fusion of the BCR and ABL genes. This is known as Philadelphia chromosome positive CML, or Ph+CML.
Treatment of CML usually includes a targeted therapy, a tyrosine kinase inhibitor (TKI), (e.g. imatinib, dasatinib or nilotinib) followed by chemotherapy if the disease progresses. Ph+ALL is a subtype of acute lymphoblastic leukaemia that carries the Ph+ chromosome that produces the fused BCR-ABL gene. It is known to have a more aggressive course than CML and is often treated with a combination of chemotherapy and TKIs. Because both of these diseases express the BCR-ABL protein, this would render them potentially susceptible to treatment with ponatinib.
For both diseases, the aim of treatment is to achieve remission of the disease by reducing the number of Ph+ leukaemia cells and achieving a major cytogenetic response (MCyR) (less than 35 percent Ph+ cells) or complete cytogenetic response (CCyR) (no Ph+ cells). A molecular response is the next aim of treatment as, even after someone has a cytogenetic response, there can still be small numbers of leukaemia cells in their blood which are undetectable by cytogenetic methods. Over time, patients may develop resistance or insensitivity to currently available targeted therapies (TKIs), impacting remission of the disease.
"New and effective treatment options are needed to help all CML patients achieve and maintain an optimal response to therapy. Over time, resistance and/or intolerance to available TKI therapies continue to be an issue for a significant group of patients," said Sandy Craine, founder and director of The CML Support Group. "Data from the PACE trial show that ponatinib continues to hold real promise as a potential therapy for more challenging cases, including patients with the multi-drug resistant T315I mutation. In our view this is very positive news for this more difficult-to-treat population."
Updated Results Presented at EHA