Ariad Pharmaceuticals said it has resumed commercial sales of its leukemia treatment Iclulsig® (ponatinib) in the United States with a narrower patient subpopulation and a new boxed warning—both designed to address concerns that drove the company to halt a Phase III trial and pull the product last year, resulting in layoffs.

Iclusig is now indicated for adult patients with refractory chronic myeloid leukemia and Philadelphia-chromosome-positive acute lymphoblastic leukemia. Iclusig was initially indicated for resistant or intolerant chronic myeloid leukemia and Philadelphia-chromosome-positive acute lymphoblastic leukemia patients.

The drug won FDA accelerated approval in December 2012, based on Phase II data—after which, Ariad began marketing the drug, while continuing clinical trials designed to add indications allowing wider use of Iclusig.

Iclusig also now carries a boxed warning advising users of possible side-effects that include vascular occlusion (including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures); heart failure (including fatalities); and hepatotoxicity, liver failure, and death.

The starting dose of Iclusig remains 45 mg daily. Ariad said it has begun shipping Iclusig to its exclusive specialty pharmacy Biologics, which has resumed filling prescriptions from physicians and distributing the cancer medicine to patients.

The changes were approved last month by the FDA as part of a revised U.S. Prescribing Information (USPI) and a communications Risk Evaluation and Mitigation Strategy (REMS) for Iclusig. The USPI and REMS allowed for immediate resumption of Iclusig’s marketing and commercial distribution some three months after the company ran afoul of the agency.

In Europe, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended approval in November of strengthened warnings on Iclusig related to patients with cardiovascular, hypertension, stroke, and vascular occlusion or thromboembolism issues.

The FDA placed a hold October 8 on the company’s Phase III EPIC or “Evaluation of Ponatinib vs. Imatinib in Chronic Myeloid Leukemia” trial of Iclusig for patients with newly diagnosed CML. Ten days later, Ariad said it mutually agreed with the FDA to terminate the trial after patients treated with Iclusig experienced increased blood clotting.

As of November 1, 2013, about 640 patients were receiving Iclusig commercially in the United States. Following the market withdrawal, the drug was made available through emergency and single-patient IND applications approved by the FDA case by case.

The FDA has approved more than 370 INDs since early November, with more than 300 patients having received Iclusig at no cost through the process.

“Ariad expects most of these patients, many of whom received a three-month supply of Iclusig, to transition from the IND program to commercial therapy by the end of the first quarter of 2014” with help from Biologics, the company stated, adding that the IND program has since been closed to new patients with Philadelphia-positive leukemias.

Biologics will further support the ARIAD Patient Access and Support Services (ARIAD PASS™) program by managing ARIAD’s reimbursement and patient access services and co-pay support programs by conducting benefits investigations and prior authorizations to assess and assist with patient eligibility.

Iclusig is priced at $125,000 for a year’s treatment—about 17% above other second-generation tyrosine kinase inhibitors, Ariad said.

In November, Ariad disclosed plans to lay off about 40% of its U.S. staff—160 employees—in across-the-board job cuts by the end of 2013. The layoffs, which shrunk Ariad’s workforce to about 295 employees in the United States and Europe, were designed to generate pre-tax savings of about $26 million in 2014.

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