Chugai Pharmaceutical Co., Ltd. has announced that F. Hoffmann-La Roche Ltd. obtained conditional marketing authorization from the European Commission (EC), for the anti-cancer agent, alectinib hydrochloride (brand name: Alecensa) for the treatment of adult patients with “anaplastic lymphoma kinase (ALK) positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or those intolerant to crizotinib.”

“Alecensa was created by Chugai, and in July 2014, Japan became the first country in the world to receive regulatory approval. We believe that the approval of Alecensa by the EC will bring great hope for patients in the EU living with this disease,” said Dr. Yasushi Ito, Chugai’s senior vice president, head of project & lifecycle management unit. “We are extremely pleased that Alecensa can contribute to the treatment of patients with ALK positive NSCLC in each country.”

EU approval was based on two clinical phase I/II trials, 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: October 24, 2014)

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. (Primary data cut-off including safety: August 18, 2014, updated Independent Review Committee (IRC) data cut-off: January 8, 2015)

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 IRC. Secondary endpoints included duration of response (DOR), progression-free survival (PFS) and safety.

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; eight percent), increased liver enzymes (alanine aminotransferase; six percent, and aspartate aminotransferase; five percent) and shortness of breath (dyspnoea; three 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. 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. Alecensa exerts its anti-tumour effect by selectively inhibiting ALK kinase activity to inhibit tumour cell proliferation and induce cell death. 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.

Chugai has out-licensed the rights of Alecensa to Roche in overseas countries including Europe and the US. Alecensa is currently approved in the United States, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India and the EU 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.