Ariad Pharmaceuticals, an oncology company, has begun Phase 3 Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC) trial of ponatinib in newly diagnosed patients with chronic myeloid leukemia (CML).
Ponatinib is an investigational pan-BCR-ABL inhibitor that also selectively inhibits certain other tyrosine kinases in preclinical studies, including FLT3, RET, KIT, FGF and PDGF receptors.
The EPIC trial is designed to evaluate the efficacy of ponatinib in comparison to imatinib based on evaluation of the primary endpoint of major molecular response (MMR) rate at 12 months.
Ariad chairman and chief executive officer Harvey Berger said the treatment of newly diagnosed CML patients has shifted in recent years to the use of second-generation BCR-ABL inhibitors.
"The EPIC trial will evaluate whether ponatinib – a pan-BCR-ABL inhibitor – produces anti-leukemic responses in these newly diagnosed patients and potentially prevents the emergence of resistance mutations seen with other tyrosine kinase inhibitors," Berger added.
Approximately 500 patients will be randomised 1:1 to standard doses of ponatinib (45mg given orally once daily) or imatinib (400mg given orally once daily).
Escalation of the imatinib dose to 600mg or 800mg per day is permitted and Ariad anticipates completing enrolment in the trial by the end of 2013.
The primary endpoint of the trial is the MMR rate at 12 months of treatment. MMR is defined as a less than or equal to 0.1% ratio of BCR-ABL to ABL transcripts on the International Scale measured in peripheral blood.
Key secondary endpoints include MMR at five years, MR at three months (a reduction in the level of BCR-ABL transcripts to 10% or less), complete cytogenetic response rate at 12 months, progression-free survival and overall survival.
Ariad chief medical officer Frank Haluska said, "The EPIC trial is powered to show the same absolute improvement in 12-month MMR rate as was seen with nilotinib in its similar trial that employed this endpoint."