Ponatinib

Chronic Myeloid Leukemia (CML) and Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

About CML and Ph+ ALL.

Chronic myeloid leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. Each year, approximately 5,000 new cases of CML are diagnosed in the United States1 and approximately 7,000 in Europe.2 The prevalence of CML is predicted to increase significantly as more patients, particularly those treated in the chronic phase of the disease, survive on current therapies.1

Treatment with BCR-ABL inhibitors is initially effective but can lead to the emergence of BCR-ABL mutations that confer drug resistance. The T315I mutant of BCR-ABL currently accounts for 15–20 percent of all drug resistance in CML. First-generation therapies for CML have been associated with resistance to other tyrosine kinase inhibitors, indicating a key unmet medical need.

Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) is a subtype of acute lymphoblastic leukemia 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.

ARIAD is conducting multiple trials evaluating ponatinib in CML. For a more comprehensive list of ponatinib clinical trials, please visit www.clinicaltrials.gov.

Phase 1/2 clinical trial in Japan

Enrollment Complete
Study Design: Randomized, open-label, multicenter
Patients: Japanese patients with chronic myeloid leukemia (CML) who have failed treatment with dasatinib or nilotinib or with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who have failed prior tyrosine kinase inhibitors. 
Purpose: To establish the recommended dose for ponatinib and confirm its anti-leukemic activity in Japanese patients. 
Locations: Multiple sites throughout Japan

Pivotal Phase 2 Study of Ponatinib in Resistant/Intolerant CML and Ph+ ALL – PACE

Enrollment Complete
Study Design: Randomized, open-label, multicenter
Patients: Heavily pretreated patients with resistant or refractory chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
Purpose: To provide definitive clinical data in patients with resistant or intolerant CML and Ph+ ALL
Location: Multiple sites worldwide


1. Kantar Health’s CancerMPact Database, 2012.
2. Rohrbacher M, Hasford J. Epidemiology of chronic myeloid leukaemia (CML). Best Pract Res Clin Haematol. 2009 Sep;22(3):295-302. Based on current estimate of population of Europe (738,199,000 in 2010).]