European Approval Sought for CML Drug Ponatinib

Ariad Pharmaceuticals followed last month’s request to the US Food and Drug Administration (FDA) for accelerated approval of the BCR-ABL inhibitor ponatinib with a similar request to the European Medicines Agency (EMA). The company, based in Cambridge, Massachusetts, is seeking marketing approval for ponatinib for patients with chronic myeloid leukemia (CML) who are resistant or intolerant to other therapies, as well as for patients with Philadelphia-chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). According to a press release, the EMA’s Committee for Medicinal Products for Human Use has already granted the company’s request for an accelerated assessment of ponatinib.

Ponatinib; source: Ariad Pharmaceuticals

“The accelerated assessment granted to our [marketing authorization application] further illustrates the major unmet medical need among patients with CML and Ph+ ALL who have become resistant or intolerant to prior tyrosine kinase inhibitor therapy,” said Ariad CEO Harvey J. Berger, MD, in the press release.

The company’s push to bring ponatinib to wide-ranging markets also continues with the initiation of a phase I/II trial at multiple centers in Japan. The phase I portion of the study will enroll at least six patients with CML who failed treatment with dasatinib or nilotinib or with Ph+ ALL in dose cohorts of 30 mg and 45 mg once daily. The phase II portion will enroll an additional 25 patients, beginning in early 2013, with a primary efficacy endpoint for chronic phase CML patients of major cytogenetic response. The primary outcome for CML patients in accelerated or blast phase, and for all Ph+ ALL patients, will be major hematologic response.

Timothy P. Clarkson, PhD, president of research and development and chief scientific officer for Ariad, said the company “anticipate[s] that this trial will confirm the results seen with ponatinib in our ongoing phase I and pivotal phase II trials.”

One such phase II study is the PACE trial, from which interim results were presented at this year’s American Society of Clinical Oncology annual meeting in Chicago in June. As Cancer Networkreported previously, 70% of patients with the T315I mutation achieved a major cytogenetic response in the PACE trial. The full analysis included 444 patients, divided into six cohorts by disease type. Of that total cohort, 267 patients were chronic-phase CML patients; 144 of these achieved a major cytogenetic response. Of all patients in the study who achieved such a response, 93% were still in MCyR after 1 year.

Ariad expects the Japanese trial will confirm this success, hopefully leading to regulatory approval in the country they say is the third-largest CML market in the world, with 1,300 new patients reported in 2010.

Ponatinib inhibits not only BCR-ABL but also several of its isoforms, potentially making it an effective treatment option in CML patients who prove resistant to existing tyrosine kinase inhibitors.