Date: 2014-12-09
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: Ariad Pharmaceuticals (USA - MA)
Product: Iclusig® (ponatinib)
Action
mechanism: Iclusig® (ponatinib) is a kinase inhibitor. Its primary target is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukaemia (CML) and Philadelphia -chromosome positive acute lymphoblastic leukaemia (Ph+ ALL). Iclusig was designed using ARIAD\'s computational and structure-based drug design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets both native BCR-ABL and isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which is a common mutation among resistant patients.
Disease: heavily pretreated patients with resistant or intolerant chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL)
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 9, 2014, Ariad Pharmaceuticals 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. 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: These data were featured in a poster presentation on December 8 at the 56th Annual Meeting of the American Society of Hematology (ASH) taking place in San Francisco .
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.
\"The long-term follow-up of results of the Phase 1 study of ponatinib in patients with chronic myeloid leukemia in the chronic phase shows that responding patients can achieve lasting, deep responses,\" said Frank G. Haluska, M.D., Ph.D., chief medical officer and senior vice president, clinical R&D at ARIAD Pharmaceuticals . \"These results inform the strategy of the planned randomized study of ponatinib doses, and the observed robust response rates and response durations support testing lower doses in refractory patients. The dose ranging study is planned to begin in 2015.\"
