ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced twelve-month follow-up data from the pivotal PACE trial of ponatinib, its investigational BCR-ABL inhibitor, in heavily pretreated patients with resistant or refractory chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The study now shows that 56 percent of chronic-phase CML patients in the trial, including 70 percent of patients with a T315I mutation, achieved a major cytogenetic response (MCyR), the primary end-point for chronic-phase CML patients.
The data are being featured today at 4:30 p.m. (ET) in an oral presentation at the 54th Annual Meeting of the American Society of Hematology (ASH) being held in Atlanta, Georgia. ARIAD filed for regulatory approval of ponatinib in the third quarter of 2012 in the U.S. and in the E.U. based on clinical data from the pivotal PACE trial.
“The 12-month results from the global PACE trial of ponatinib reinforce its impressive anti-leukemic activity in heavily pretreated CML patients, regardless of their mutation status or disease stage,” stated Jorge Cortes, M.D., professor and deputy chair, Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
“Ponatinib demonstrated early responses in chronic-phase patients with thirty-four percent of these patients achieving a major molecular response and fifteen percent of those patients achieving a complete molecular response,” he added. “Of particular importance, responses to ponatinib appear to be durable, with 91 percent of chronic-phase CML patients projected to remain in major cytogenetic response at one year.”
- Trial Design
- Efficacy data were reported at ASH on 444 treated patients in six pre-specified cohorts at 45 mg of ponatinib administered orally once daily, including 267 patients with chronic-phase CML. Findings were based on a minimum follow-up of 12 months in patients remaining on study.
- Ninety-three percent of the patients in the trial had received at least two tyrosine kinase inhibitors prior to enrollment. Fifty-eight percent of the patients had received three or more tyrosine kinase inhibitors prior to enrollment.
- Chronic-phase patients had bone marrow assessments approximately every three months for determination of cytogenetic response.
- Chronic-phase CML patients evaluable for cytogenetic response (N=267)
- Based on assessment of all evaluable chronic-phase patients in the trial, 56 percent (149 of 267) of patients achieved a MCyR, with 46 percent achieving a complete cytogenetic response (CCyR). The median follow up of the chronic-phase CML patients is 15.3 months.
- Of the 64 evaluable chronic-phase CML patients with the T315I mutation, 70 percent (45 of 64) of these patients achieved a MCyR, with 66 percent achieving a CCyR. The MCyR rate in evaluable chronic-phase patients without the T315I mutation was 51 percent (104 of 203).
- Thirty-four percent (91 of 267) of chronic-phase CML patients achieved a major molecular response (MMR).
- Fifteen percent (39 of 267) of chronic-phase CML patients achieved a 4.5-log reduction of BCR-ABL transcripts (MR4.5).
- Responses in chronic-phase patients who had received only one prior TKI (N=19)
- There were 19 chronic-phase patients treated with ponatinib in the PACE trial who had previously received only one tyrosine kinase inhibitor (TKI). Thirteen of these patients had previously been treated with imatinib only, and six had previously received either dasatinib or nilotinib. Of these 19 patients, 84 percent (16 of 19) achieved a MCyR.
- Safety profile (N=449)
- The most common non-hematologic treatment-emergent adverse events in the PACE trial included rash (in 38% of patients), abdominal pain (38%), headache (35%), dry skin (35%), and constipation (34%), with the majority of these being grades 1 or 2 in severity.
- The most common hematologic treatment-emergent adverse events were thrombocytopenia (42%), neutropenia (24%), and anemia (20%), which were primarily grades 3 or 4 in severity.
- Pancreatitis and pneumonia were the most common non-hematologic treatment-emergent serious adverse events (5% each), followed by abdominal pain (4%), myocardial infarction (3%), congestive heart failure (3%), atrial fibrillation (3%), and pyrexia (3%). The most common hematologic serious adverse events were anemia, febrile neutropenia, and thrombocytopenia (3% each).
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