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ARIAD Announces Discontinuation of the Phase 3 Epic Trial of Iclusig in Patients with Newly Diagnosed Chronic Myeloid Leukemia

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 18, 2013-- ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA) today announced that it is discontinuing the Phase 3 EPIC (Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia) trial of Iclusig® (ponatinib) in patients with newly diagnosed chronic myeloid leukemia. ARIAD and the U.S. Food and Drug Administration mutually agreed that the trial should be terminated because arterial thrombotic events were observed in patients treated with Iclusig. This decision was made in the interest of patient safety based on a recent assessment of data in the clinical trial.

“Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,”stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. "We believe that this is in the best interests of patient safety and the overall development of Iclusig.”

Patients in the EPIC trial are being removed from treatment and will be transferred to the care of their physician. ARIAD announced in early September that fifty percent of patients, or approximately 264 patients, had been enrolled in the EPIC trial by that time. Final enrollment is 307 patients.

The EPIC trial was a randomized, two-arm, multicenter trial that sought to compare the efficacy of ponatinib with that of imatinib in adult patients with newly diagnosed CML in the chronic phase. The trial was being conducted at approximately 150 investigational sites in more than 20 countries. Patients in the trial had to be at least 18 years of age and diagnosed with CML within six months prior to enrollment. Approximately 500 patients were to be randomized 1:1 to the standard dose of ponatinib (45 mg given orally once daily) or imatinib (400 mg given orally once daily). Increasing the imatinib dose to 600 mg or 800 mg per day was permitted. The primary endpoint of the trial was major molecular response at 12 months of treatment.

Iclusig is commercially available in the U.S. and EU for patients with resistant or intolerant CML and Philadelphia-chromosome positive acute lymphoblastic leukemia. ARIAD continues to work with health authorities to make appropriate changes to the Iclusig product labeling to reflect the recently announced safety findings from the pivotal PACE trial that was the basis of its marketing approvals.

Information for patients and physicians

For more information about the changes in Iclusig clinical trials, patients and physicians should visit www.clinicaltrials.gov, call the ARIAD U.S. toll-free number (855) 552-7423, the EU toll-free number 800 00027423, or the international number +1 (617)-503-7423. Patients and doctors may e-mail inquiries to medinfo@ariad.com.

http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-newsArticle&ID=1...

Does this mean that all patients who were doing well on Ponatinib now have to come off it and find something else - or just those on the trial?

What about those with the T315i mutation? Surely if they're doing well, they can keep on taking it and wouldn't have been part of the EPIC trial anyway?

I take it that the marketing authorisation hasn't been rescinded. Just that the trial has been stopped.

David as I understand it this trial which has been stopped was looking at Ponatinib as a first line treatment compared to Imatinib. People who have gone on to Ponatinib have in the main tried imatinib (or other TKIs) as a first line treatment and it has for some reason (e.g. T315i, non-response, side effects) not worked for them. The trial has been stopped because Ponatinib has introduced a risk not seen to anything like the same extent with Imatinib. So I would not expect it to cause a rush to change those for whom Ponatinib is working where other TKIs didn't, as the risk identified in the trial is a lot less than the risk of leaving CML without an effective treatment.

Hi David,

As far as I understand it, the EPIC trial has ceased to recruit any more patients owing to the adverse event seen in some trial patients. Those already treated with ponatinib who are doing well will be re-evaluated and their doses will be subject to reduction. For example treatment with the standard dose of 45mg daily will be reduced to 30mg... 30mg will be reduced to 15mg and I assume those on 15mg will stay at that low dose. Obviously this is a concern and clinicians will need to keep a close eye on their patients, especially for irreversible adverse cardiovascular events.
As Alastair has indicated, those with either the T315i mutation, or lack of response to other TKIs, have little choice but to stay the course with ponatinib- hence the dose reductions- as the only other option at the moment is an SCT.

see Ariad's press release on EPIC trial:

nvestor conference call today, October 18th, at 8:30 a.m. E.T.

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA) today announced that it is discontinuing the Phase 3 EPIC (Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia) trial of Iclusig® (ponatinib) in patients with newly diagnosed chronic myeloid leukemia. ARIAD and the U.S. Food and Drug Administration mutually agreed that the trial should be terminated because arterial thrombotic events were observed in patients treated with Iclusig. This decision was made in the interest of patient safety based on a recent assessment of data in the clinical trial.

Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. "We believe that this is in the best interests of patient safety and the overall development of Iclusig.

Patients in the EPIC trial are being removed from treatment and will be transferred to the care of their physician. ARIAD announced in early September that fifty percent of patients, or approximately 264 patients, had been enrolled in the EPIC trial by that time. Final enrollment is 307 patients.

The EPIC trial was a randomized, two-arm, multicenter trial that sought to compare the efficacy of ponatinib with that of imatinib in adult patients with newly diagnosed CML in the chronic phase. The trial was being conducted at approximately 150 investigational sites in more than 20 countries.

http://seekingalpha.com/news-article/7890872-ariad-announces-discontinua...

Sandy

Link attached. http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm

See Home page for this article and the FDA statement.

Sandy