Otsuka Pharmaceutical Co., Ltd.

January 8, 2016

Otsuka and ARIAD Announce New Drug Application for Ponatinib Submitted in Japan for the Treatment of Refractory Leukemia

  • Ponatinib (generic name) is a tyrosine kinase inhibitor discovered by ARIAD Pharmaceuticals in the United States. The New Drug Application (NDA) for ponatinib was filed in Japan for the first time as a novel oral treatment for chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
  • Ponatinib (brand name outside Japan is Iclusig®) is already being marketed in Europe and the United States as a treatment for patients with refractory chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL), and is awaited in Asian countries including Japan.
  • Otsuka obtained rights in December 2014 to co-develop and commercialize ponatinib in Japan and nine other Asian countries.*1

Otsuka Pharmaceutical Co., Ltd. (Headquarters: Chiyoda-ku, Tokyo; President and CEO: Tatsuo Higuchi; "Otsuka") has filed the NDA in Japan for "ponatinib (brand name outside Japan is Iclusig®), a known tyrosine kinase inhibitor (TKI) developed by ARIAD Pharmaceuticals, Inc. (Headquarters: Massachusetts, United States; "ARIAD") used to treat resistant and intolerant chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).*2

ARIAD conducted a multicenter Phase I / II trial in Japan to confirm efficacy, safety and tolerability of ponatinib. Otsuka filed the NDA based on these results and the results of overseas clinical trials. Furthermore, ponatinib was designated in Japan to be an orphan drug in September 2015.

Traditional Treatment (TKI) and Treatment Resistance due to Mutation / Efficacy of Ponatinib on T315I Mutations

Ponatinib is a TKI discovered and developed by ARIAD that targets BCR-ABL expressed in CML and Ph+ ALL. This drug is a new chemically synthesized oral TKI, and is specifically designed to inhibit unmutated BCR-ABL as well as T315I mutation, a mutant-type BCR-ABL that manifests and induces resistance after patients are treated with other TKIs. Ponatinib demonstrates efficacy in currently available TKI-resistant and in patients who are intolerable CML as well as relapsed or refractory Ph+ ALL, but it also demonstrates efficacy for isoforms of BCR-ABL that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs. Ponatinib was approved by the US FDA in December 2012, and was approved in Europe in July 2013.

In Japan, CML occurs in approximately 1 out of 100,000 people among all age groups. It is estimated that there are approximately 11,000 patients.*3 Although the mortality rate has decreased with the advancement of TKI treatment, the number of patients is steadily increasing with an aging population. Initial symptoms are rarely seen in CML patients from disease onset to the chronic phase (5-6 years); however, white blood cell count and the blast cell ratio increase and, as the disease progresses, patients begin experiencing symptoms such as general malaise, weight loss, and bloating due to hepatosplenomegaly. In the accelerated phase (6-9 months), patients experience bone pain and exacerbation of hepatosplenomegaly; in the blast phase (3-6 months), patients experience anemia, bleeding tendencies, infections, etc. For CML, symptoms gradually worsen and risk of treatment resistance increases as the disease progresses*4. In contrast, Ph+ALL is seen in pediatric and elderly patients, and prognosis is extremely poor for patients who relapse after receiving initial ALL treatment and is an area where needs are still unmet.*5,6

Although TKI is used as a first-line drug for CML and Ph+ ALL, resistance to treatment can develop as the disease progresses because of amplification, overexpression or mutation of BCR-ABL genes, which are causal factors of the disease. In such cases, an adequate patient response to therapy may not be obtained even after several TKI products are used. In addition, there are patients who must discontinue treatment as they become intolerant of the side effects of other TKIs. A new TKI treatment is desired in Japan and other Asian countries in order to treat such resistant or intolerant patients.

Otsuka is currently expanding its product portfolio and is focusing on CNS (neuropsychiatry), cardiovascular, ophthalmology, and oncology fields. The company will continue to develop and commercialize pharmaceuticals aimed to improve survival of hematological cancer patients with insufficient treatment options by undertaking operations to provide a wide range of products from diagnostics to treatment.