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| Oct 27, 2011
The approval of Halaven® (eribulin, Eisai) for progressive breast cancer in the United States (November 2010), Europe (March 2011), and Japan (April 2011) over a six month period signaled the impact of a growing number agents that Japanese pharmaceutical companies are introducing to global oncology markets.
The next two agents originally developed in Japan (to focus on Japanese patients) that are about to enter pivotal studies in the West include TAS-102 (Taiho) and KW-0761 (mogamulizumab, Kyowa Hakko Kirin). Both will enter into pivotal studies in Western populations based on initial strong efficacy signals in the Japanese studies.
A randomized Phase II trial in Japanese patients suggested that TAS-102 has a future role in refractory metastatic colorectal cancer (mCRC) after all approved agents are exhausted (essentially third- or fourth-line). TAS-102 increased median survival from 6.6 months to 9.0 months (p=0.0011). Median progression-free survival (PFS) survival was also significantly increased from 1.0 to 2.0 months according to an independent review (p<0.0001). The primary anti-tumor benefit came in the form of disease control (43.8% versus 10.5%) with only one patient achieving a partial response to TAS-102.
Taiho has suggested that it will investigate TAS-102 in a global Phase III trial enrolling Japanese, North American, and European patients. The indication that Taiho is pursuing with TAS-102 has received a lot of attention recently as a real unmet need in colorectal cancer. KRAS wild-type patients have more options available to them, specifically the EGFR antibodies, putting the “frontier of refractory disease” essentially in fourth line. For KRAS-mutant patients, the “frontier of refractory disease” is third-line. There are two agents in Phase III focusing on his indication: BAY 73-4506 (regorafenib, Bayer/Onyx) and perifosine (Aeterna Zentaris/Keryx). Bayer announced via press release on October 27, 2011, that BAY 73-4506 met its primary endpoint by improving overall survival compared to placebo in its pivotal Phase III trial.
The other agent out of Japan to watch is KW-0761, which could become for T-cell lymphoma what Rituxan® (MabThera in Europe, rituximab, Roche/Chugai) has become for B-cell lymphoma. KW-0761 is an antibody directed against CCR4 which is widely expressed on T cells much like CD20 (Rituxan’s target) is expressed on B cells.
B-cell lymphoma represents the overwhelming majority of lymphoma patients. T-cell lymphoma represents approximately 10% of lymphoma in Western populations and perhaps as much as 20% in Japan depending on the data source. The market potential for KW-0761 is smaller than Rituxan, but the sheer number of lymphoma patients worldwide still makes the potential for this agent appealing.
In April 2011, Kyowa Hakko Kirin announced that it filed a new drug application in Japan for relapsed adult T-cell leukemia/lymphoma based on a strong overall response which was 50% including a 32% complete response rate (Ishida, Abstract IS-5-4, Japanese Society of Medical Oncology, 2011). This data and physician enthusiasm suggest that KW-0761 could soon be approved for relapsed adult T-cell leukemia/lymphoma (ATL) in Japan but also might have a wider role in T-cell lymphoma in Western populations and also in cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL) with several trials currently ongoing.