ARIAD announces changes in Iclusig product labeling to reflect updated safety information

Oct 9 2013

ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced results of its review of updated clinical data from the pivotal PACE trial of Iclusig^® (ponatinib) and actions that it is taking following consultations with the U.S. Food and Drug Administration (FDA).

• With a median follow up of 24 months, serious arterial thrombosis occurred in 11.8% of Iclusig-treated patients: cardiovascular events 6.2%, cerebrovascular events 4.0% and peripheral vascular events 3.6% (some patients had more than one type of event). This compares to 8.0% after 11 months of follow up reflected in the current U.S. prescribing information.
• At 24 months, serious venous occlusion occurred in 2.9% of Iclusig-treated patients, compared to 2.2% in the current U.S. prescribing information.
• The incidence rate of the arterial thrombotic events when normalized to duration of treatment exposure has not increased (10.0 events/100 patient-years in the original analysis and 9.6 events/100 patient-years in the current analysis).
• Non-serious and serious arterial and venous adverse events combined occurred in approximately 20% of Iclusig-treated patients.

The Company is implementing the following actions in its Iclusig clinical development program:

• Patient enrollment in all clinical studies of Iclusig is being paused, and subject to agreement with the FDA, will be resumed with anticipated changes in dose and other modifications. In concert with this action, the FDA placed a partial clinical hold on all new patient enrollment in clinical trials of Iclusig.
• Patients who are currently receiving Iclusig in clinical trials will continue on therapy. Reductions in Iclusig dose from 45 mg daily will be implemented on a trial-by-trial basis for patients whose Iclusig treatment is ongoing.
• The dose of Iclusig in patients who are currently enrolled in the EPIC trial will be reduced to 30 mg daily unless they have achieved a major molecular response or reach one in the future, in which case the dose will be further reduced to 15 mg daily. The Data Monitoring Committee of the EPIC trial has endorsed these changes.
• The eligibility criteria for Iclusig clinical trials will be modified to exclude patients who have experienced prior arterial thrombosis resulting in heart attack or stroke.

The PACE trial data demonstrate continued efficacy after dose reduction. Of 270 chronic-phase patients in the pivotal study, 190 patients dose reduced to either 30 mg or 15 mg. Of 110 (58%) patients who initially achieved a major cytogenetic response (MCyR), over 90% of these patients maintained this response after a median follow up of 19 months, despite dose reduction. Of 35 patients who achieved a MCyR and subsequently were reduced to 15 mg, all but 2 patients maintained the response.

At this time, the U.S. prescribing information for Iclusig is unchanged. Iclusig continues to be available in the U.S. to patients with resistant or intolerant chronic myeloid leukemia and Philadelphia-chromosome positive acute lymphoblastic leukemia in the commercial setting at the approved, once-daily dose of 45 mg. ARIAD has been in consultation with the FDA and other health authorities about changes in Iclusig product labeling to reflect the updated information.

ARIAD is sending a written communication to healthcare providers. It also is informing the European Medicines Agency and other regulatory agencies of today's decisions. ARIAD understands that the FDA is planning to issue a Drug Safety Communication on Iclusig this week.

"We believe that the actions we are taking will help us ensure the most appropriate and safe use of Iclusig. With two years of follow up, we have learned a great deal about both the efficacy and safety of Iclusig in patients with Philadelphia-positive leukemias," stated Harvey J. Berger, M.D., chairman and chief executive officer of ARIAD. "We are focused first and foremost on the needs of cancer patients - to have new medicines that provide both safe and effective treatment of their malignancies. Our unwavering commitment to patients has led us to promptly take the steps we have outlined."

Investor and analyst briefing and webcast

ARIAD management will host a conference call and webcast to discuss these actions today, October 9, at 8:30 a.m. ET. The live webcast can be accessed by visiting the investor relations section of the Company's website at http://investor.ariad.com. The call can be accessed by dialing (800) 299-8538 (U.S.) or +1 (617) 786-2902 (international) and providing the participant code 20840481. A replay of the call will be available on the ARIAD website approximately two hours after completion of the call and will be archived for three weeks.

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 [email protected].