ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced publication of results from the Phase 1 study of ponatinib, its investigational, tyrosine kinase inhibitor in heavily pretreated patients with resistant and refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The paper was published today in the New England Journal of Medicine (Vol. 367, No. 22, Pages 2075-88). The article is accompanied by an editorial by John M. Goldman, D.M., F.R.C.P. of the Department of Haematology, Imperial College London (Pages 2148-49). The Phase 1 dose-escalation study of ponatinib enrolled 81 patients with resistant hematologic cancers, including 60 patients with CML and five patients with Ph+ ALL. With median follow-up at 73 weeks, 72 percent of patients (31 of 43) with chronic-phase CML enrolled in the study had a major cytogenetic response (MCyR), including 92 percent (11 of 12) who had the T315I gatekeeper mutation, which is the most common mutation among resistant patients. It was estimated that 89 percent of patients with chronic-phase CML who had a MCyR would remain in response at 1 year (95% confidence interval, 69% to 96% by Kaplan–Meier analysis). Of 22 patients with accelerated-phase or blast-phase CML or Ph+ ALL, 36 percent (8 of 22) had a major hematologic response, and 32% (7 of 22) had a MCyR. Dose-limiting toxicities reported in the study included elevated lipase or amylase levels and pancreatitis. The most common treatment-related adverse events included rash (32%), thrombocytopenia (27%), arthralgia (17%), increased lipase (15%), fatigue (14%), acneiform dermatitis (14%), dry skin (14%), and nausea (14%). Neutropenia, headache, hypertriglyceridemia and myalgia occurred less frequently. The incidence of pancreatitis was 14% across all dose levels in the trial. The onset of pancreatitis, elevated amylase, and elevated lipase was dose-related with regard to both incidence and timing. “These findings demonstrate that ponatinib is a highly active agent in patients with CML who had become resistant to one or more tyrosine kinase inhibitors,” stated Jorge Cortes, M.D., professor and deputy chair, department of leukemia, The University of Texas M.D. Anderson Cancer Center. “The response rates observed in this study confirm substantial and durable clinical activity and suggest that ponatinib may overcome BCR-ABL mutation-based resistance, as well as resistance when no mutations are detectable.”
About PonatinibInternally 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. The primary target for ponatinib is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Ponatinib was designed using ARIAD’s computational and structure-based drug design platform to inhibit the activity of BCR-ABL with 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. About CML and Ph+ ALL 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 ALL, which 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 susceptible to treatment with ponatinib. About ARIAD 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. ARIAD’s approach to structure-based drug design has led to several internally discovered, molecularly targeted medicines for drug-resistant or difficult-to-treat cancers, including chronic myeloid leukemia and non-small cell lung cancer. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm). This press release contains “forward-looking statements” including, but not limited to, statements relating to the clinical data for ponatinib, submission, review, and potential approval of the NDA, and timing of other regulatory filings for marketing approvals. Forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.