ARIAD Pharmaceuticals has announced that Iclusig (ponatinib) was approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for the treatment of chronic myeloid leukemia (CML) resistant or intolerant to previous drug treatment, as well as for relapsed or treatment-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).
The approval will trigger a $10 million milestone payment to ARIAD from Otsuka Pharmaceuticals, under a December 2014 agreement.
“Our collaboration with Otsuka has resulted in today’s approval of Iclusig in Japan, providing an important new treatment for patients with refractory CML and Ph+ ALL,” Paris Panayiotopoulos, ARIAD’s president and chief executive officer, said in a press release. “Japan represents a large market opportunity for Iclusig and its first approval in Asia. We are committed to expanding patient access and to continuing our successful partnership with Otsuka as evidenced by recent marketing applications for Iclusig submitted in Korea and Taiwan.”
Iclusig is a kinase inhibitor that targets particularly the BCR-ABL protein (an abnormal tyrosine kinase expressed in CML and Ph+ALL). The drug was designed using ARIAD’s computational and structure-based drug-design platform specifically to inhibit BCR-ABL activity. Iclusig targets not only native forms of the abnormal tyrosine kinase but also its isoforms, which carry mutations that confer resistance to treatment – including the T315I mutation, which has been linked to resistance to other approved tyrosine kinase inhibitors (TKIs).
In the United States, Iclusig is approved for the treatment of patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ALL; and for the treatment of adult patients with chronic phase, accelerated phase, or blast phase CML or Ph+ALL for whom no other TKIs are indicated.
”Treatment failure affects a substantial proportion of CML patients treated with tyrosine kinase inhibitors due to resistance or intolerance. For these patients living with CML in Japan, we are grateful to have Iclusig as a new approved treatment option,” said Arinobu Tojo, MD, PhD, deputy director of the Research Hospital at the Institute of Medical Science at the University of Tokyo.
The PMDA approved Iclusig based on results of a Phase 1/2 study in Japanese patients, and on results from the international pivotal PACE and Phase 1 trials of Iclusig.
The Japanese Phase 1/2 study, which enrolled 35 patients with CML or Ph+ALL whose previous treatment with TKIs had failed, confirmed that Iclusig has anti-leukemic activity in this patient population. After a median follow-up of 14.9 months, the study found that, among the 17 patients in chronic phase, 65 percent achieved the primary efficacy endpoint of major cytogenetic response, and 35 percent recorded major molecular responses.
The most frequently reported side effects were decreased platelet and neutrophil counts, fever, hypertension, dry skin, and rashes. Atherosclerostic events deriving from the treatment were also reported in four patients (11%). In total, 13 patients had to remain on therapy, including 12 in the chronic phase, as their required median duration of response was not reached at the time of evaluation.
Iclusig is not indicated nor recommended for the treatment of patients with newly diagnosed chronic phase CML.
Besides the U.S. and Japan, Iclusig has also been approved in the European Union, Australia, Canada, Israel, Switzerland.