ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced long-term follow up data from the Phase 1 trial of Iclusig ® (ponatinib), its approved BCR-ABL inhibitor, in heavily pretreated patients with resistant or intolerant chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The study now shows that with a median follow-up of four years in chronic phase CML (CP-CML) patients, Iclusig continues to demonstrate anti-leukemic activity in patients with limited treatment options and that responses have been maintained in CP-CML patients (n=43) with 72 percent having a major cytogenetic response (MCyR), 65 percent having a complete cytogenetic response (CCyR) and 56 percent having a major molecular response (MMR). Long-term safety data show that careful benefit-risk evaluations should guide decisions to use and maintain ponatinib therapy, particularly in patients who may be at increased risk for arterial thrombotic events. These data were featured in a poster presentation on December 8 at the 56 th Annual Meeting of the American Society of Hematology (ASH) taking place in San Francisco. "With nearly six years of treatment for some patients in this study, ponatinib continues to demonstrate anti-leukemic responses in this heavily pre-treated patient population," stated Moshe Talpaz, M.D., Associate Director of Translational Research and Associate Chief of Hematologic Malignancies, Trotman Professor of Leukemia Research, at the University of Michigan Comprehensive Cancer Center. "We are continuing to assess the safety profile of ponatinib and the impact of dose reductions of ponatinib for patients with CML and Ph+ ALL for whom the need and potential benefit outweigh the risk." Phase 1 Trial Long-Term Data The Phase 1 dose-escalation study of ponatinib (starting dose range: 2 to 60 mg once daily) enrolled 81 patients with resistant or refractory hematologic cancers, including 43 patients with chronic-phase CML. Sixty percent of CP-CML patients in this study had failed at least three prior tyrosine kinase inhibitors (TKI), and over 90 percent received at least two prior TKIs. Twenty-two CP-CML patients (51 percent) remain on study. Data presented at ASH focus on these CP-CML patients and represent follow-up through September 26, 2014.
- Median follow-up for CP patients is now four years (49.9 months) with the maximum follow-up now six years (69.9 months).
- Of 22 ongoing CP patients, 14 are receiving 15 mg/day ponatinib, 5 are at 30 mg/day, and 3 are at 45 mg/day. The mean current dose is 22.5 mg/day, and, the median dose intensity in these patients during the course of the study is 34.2 mg/day.
- Anti-leukemic activity continues to be observed with ponatinib treatment:
- 72 percent of CP patients had a MCyR, 65 percent had a complete cytogenetic response (CCyR) and 56 percent had a MMR. Of note, 17/22 ongoing CP-CML patients (77 percent) are in deep molecular response of MMR or better;
- The median time to MCyR, CCyR and MMR was 2.8, 5.5 and 7.4 months, respectively;
- Median duration of MCyR, CCyR or MMR have not yet been reached.
- By Kaplan-Meier analysis, the probability of CP-CML patients maintaining MCyR at 4 years was estimated as 68 percent.
- Ten of the 15 CP patients (67%) who started ponatinib at a dose of 30 mg or less achieved MCyR, comparable to the overall response rate of 72 percent.
- The most common treatment-emergent adverse events occurring in CP patients were rash (65%), fatigue (60%), abdominal pain (58%), headache (58%), and arthralgia (53%). When analyzed by year, most adverse events occurred in the first year of treatment.
- Thirty percent (n=13) of CP patients experienced arterial thrombotic serious adverse events (SAEs), and 40 percent of CP-CML patients experienced any arterial thrombotic event, independent of severity. There were two venous thrombotic events and no serious venous thrombotic events.
About Iclusig ® (ponatinib) tabletsIclusig is approved in the U.S., EU, Switzerland and Australia. In the U.S., Iclusig is a kinase inhibitor indicated for the:
- Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
- Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.
- Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.
- Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.
Iclusig ® is a registered trademark of ARIAD Pharmaceuticals, Inc.