On February 27, 2017 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that Chugai Pharma Taiwan Ltd., a wholly owned subsidiary of Chugai, obtained approval from the Taiwan Food and Drug Administration (TFDA), for the anti-cancer agent, alectinib hydrochloride (brand name: Alecensa) for the treatment of people with "anaplastic lymphoma kinase (ALK) positive, advanced non-small cell lung cancer (NSCLC) who have progressed on or those intolerant to crizotinib (Press release, Chugai, FEB 26, 2017, View Source [SID1234517856])."

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"We believe that the approval of Alecensa by the TFDA would bring the great news to Taiwanese patients who are fighting against this disease," said Dr. Yasushi Ito, Chugai’s Senior Vice President, Head of Project & Lifecycle Management Unit. "We are pleased that Alecensa created by Chugai will contribute to the treatment of ALK-positive NSCLC."

Taiwan’s approval was based on two clinical phase I/II studies, as summarised below:

– The NP28761 study is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib. (Data cut-off: January 22, 2016)

– The NP28673 study is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of Alecensa in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib. (Data cut-off: February 1, 2016)

– People in the phase II studies received 600 mg of Alecensa orally twice daily. In both trials, the primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1), and evaluated by an Independent Review Committee (IRC). Secondary endpoints included duration of response (DOR) and safety.

– Efficacy Parameters

The NP28761 study (N=87) The NP28673 study (N=138)
IRC Assessment Investigator Assessment IRC Assessment Investigator Assessment
ORR (%)
(95% CI) 42.5
(32.0-53.6) 52.9
(41.9-63.7) 44.9
(36.5-53.6) 51.4
(42.8-60.0)
DOR (median in months)
(95% CI) 14.9
(7.5-NE)
13.3
(8.8-18.2)
15.2
(11.2-24.9)
15.2
(11.0-20.3)
– Alecensa demonstrated a safety profile consistent with that observed in previous studies.

– The most common Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; five percent), increased liver enzymes (alanine aminotransferase; 4.8 percent, and aspartate aminotransferase; 3.6 percent) and shortness of breath (dyspnoea; 3.6 percent).

Alecensa is a highly selective oral ALK inhibitor discovered by Chugai. It has been reported that approximately five percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene.1) ALK kinase signalling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumour cells and transforming the cells into tumour cells.2, 3) Alecensa exerts its anti-tumour effect by selectively inhibiting ALK kinase activity to inhibit tumour cell proliferation and induce cell death.4) In addition, Alecensa is not recognized by the active efflux system in the blood brain barrier which actively pumps molecules out of the brain. Alecensa is able to remain active in the central nervous system and has proven activity against brain metastases.

Alecensa is currently approved in the United States, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, the EU and Taiwan for the treatment of advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In Japan, Alecensa is available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" and is marketed by Chugai.

1) Biomarker committee of The Japan Lung Cancer Society, Guidelines for ALK gene tests in lung cancer patients
2) Soda et al., Nature. 448: 561-566 (2007)
3) Takeuchi et al., Clin Cancer Res. 15: 3143-3149 (2009)
4) Sakamoto et al., Cancer Cell. 19: 679-690 (2011)