ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced safety and efficacy follow-up data on Iclusig ® (ponatinib), its approved BCR-ABL inhibitor, in patients with a baseline T315I mutation from its Phase 1 and Phase 2 PACE trials in heavily pretreated patients with resistant or intolerant chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). With a median follow-up of three years for CP-CML patients and nine months overall, Iclusig continues to exhibit responses in patients with the T315I mutation, for whom there is no other approved tyrosine kinase inhibitor (TKI) therapy. Among patients with the T315I mutation, major cytogenetic response (MCyR) was achieved by 92 percent (11/12) of chronic phase CML patients (CP-CML) in the Phase 1 trial and 72 percent (46/64) of CP-CML patients in the PACE trial; taken together, the combined MCyR rate for all T315I CP-CML patients was 75 percent. 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 on Monday December 8, at the 56 th Annual Meeting of the American Society of Hematology (ASH) taking place in San Francisco. "For CML patients with the T315I mutation, there were few treatment options available prior to ponatinib, and prognosis for these patients was poor. Now, with nearly six years of treatment for some patients in these trials, we have longer term data demonstrating that ponatinib continues to evoke responses in these CP-CML patients," stated Michael J. Mauro, M.D., Leader, Myeloproliferative Neoplasms Programs, at the Memorial Sloan Kettering Cancer Center. "With these follow-up data, overall survival of 78 percent is now estimated at three years for chronic-phase patients with the T315I mutation in these trials." Phase 1 and PACE Data in Patients with T315I The analysis describes the pooled efficacy and safety of ponatinib in patients with a T315I mutation detected at baseline from the ongoing Phase 1 dose-escalation study and Phase 2 PACE trials. The analysis includes 147 patients with a T315I mutation from the Phase 1 (n=19) and PACE (n=128) trials. Half of the 76 CP-CML patients with T315I remain on treatment and 44 (30%) total patients (all disease phases) with T315I remain on treatment in the respective trials. Data presented on these patients are as of September 26, 2014 for the Phase 1 trial and October 6, 2014 for the PACE trial.
- Median follow-up for all T315I patients in this analysis is 8.9 months. The median follow-up for CP-CML patients with T315I (n=76) is three years (maximum follow-up, 70 months).
- In these heavily pre-treated T315I patients, 45 percent of the total patients had received treatment with two prior TKIs, and 40 percent had received three or more prior TKIs. In patients with CP-CML, 46 percent had received two prior TKIs, and 39 percent had three or more prior TKIs.
- For CP patients, responses continue to be observed in T315I patients treated with ponatinib at 3 years. In the combined analysis of these patients from both trials:
- 75 percent of all CP-CML patients achieved MCyR, 72 percent achieved a complete cytogenetic response (CCyR), and 61 percent achieved a major molecular response (MMR).
- By Kaplan-Meier estimate, 83 percent of these CP patients were estimated to maintain MCyR at 3 years, and 81 percent were estimated to maintain CCyR at 3 years. The median duration of response has not yet been reached.
- 58 percent of advanced phase (AP) CML patients with T315I achieved major hematologic response (MaHR), the end-point for those patients in the trials. Twenty-seven percent of blast phase (BP) CML patients, and 38 percent of Ph+ ALL patients achieved MaHR.
- The probability for overall survival in CP patients with T315I at 36 months is 78 percent and 63 percent for patients with AP-CML.
- The most common treatment-emergent adverse events in T315I patients (all disease phases) were rash (42%), abdominal pain (39%), headache (39%), and nausea (36%). The most common serious treatment-emergent adverse events were neoplasm progression (10%), pneumonia (7%), and acute myocardial infarction (5%).
- Thirty-two percent (n=24) of CP-CML patients with T315I experienced arterial thrombotic events, and 7 percent experienced a venous thrombotic event (VTE). Exposure-adjusted incidences of arterial and venous thrombotic events in patients with the T315I mutation were similar to those observed in the overall patient population.
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.