Following a decision earlier this year to stop early a comparative Japanese Phase III trial with its oral ALK inhibitor Alecensa (alectinib) on highly positive results, Chugai Pharmaceutical Co. Ltd.will present new data from the study at the upcoming ASCO meeting.

The J-ALEX open-label program compared the drug in the first-line treatment of patients with anaplastic lymphoma kinase (ALK) fusion gene-positive, advanced or recurrent non-small cell lung cancer (NSCLC) with Pfizer Inc.'s ALK inhibitor Xalkori (crizotinib).

The 207 participants, allocated equally to both drug arms, had either not received chemotherapy or had undergone just one chemotherapy regimen, and were all ALK inhibitor naïve.

The study was halted ahead of schedule in February after better than expected results and a determination by the independent data monitoring committee that it had already met the primary endpoint of progression-free survival (PFS) at interim analysis ([A#28160210001]).

In new primary findings to be presented in oral abstract form to the ASCO (American Society of Clinical Oncology) meeting in Chicago from June 3-7, Chugai said there was a significant extension in PFS for alectinib.

The PFS hazard ratio of the alectinib arm to the crizotinib arm was 0.34 and alectinib demonstrated significantly prolonged PFS (99.7% confidence interval: 0.17-0.70; stratified log-rank p<>

Median PFS was not reached in the alectinib arm but was 10.2 months (95% CI: 8.2-12.0) in the crizotinib arm.

Side-Effect Profile

The Chugai drug also appears to have a favorable side-effect profile compared with crizotinib. The main adverse event in the alectinib group was constipation, affecting 36% of patients with more than 30% frequency, while a broad range of adverse events including nausea and diarrhea occurred in the crizotinib group at over 30% frequency.

Overall, Grade 3-4 adverse effects occurred in 27% of patients in the alectinib arm and in 51% of those on crizotinib, with no treatment-related deaths in either group.

"The J-ALEX study…demonstrated superiority of Alecensa over standard therapy for the first time in the world. This finding not only greatly encourages the patients suffering from ALK fusion gene positive NSCLC but also illustrates the high level of drug development progression from basic research to clinical studies in Japan," Chugai EVP Dr. Yutaka Tanaka said in a statement.

The number of newly diagnosed lung cancer patients in Japan is around 115,000 annually, with NSCLC accounting for around 80% of primary lung cancers.

Some 2-5% of NSCLC patients express a chromosomal arrangement that causes the ALK gene to fuse with another gene, which causes constantly active ALK signaling in affected cells, leading to uncontrollable growth.

Japanese Roots

Chugai - part of the Roche group - also pointed to the early research on the role of the ALK gene that had been conducted in Japan, which became the first market worldwide to approve Alecensa in July 2014, for second-line use in the orphan indication of ALK-positive unresectable, recurrent/advanced NSCLC.

Xalkori was launched in this setting in Japan in May 2012, while Alecensa was approved in the US in December through Genentech (Roche), based on Phase I/II data, as a Breakthrough Therapy-designated drug for ALK-positive metastatic NSCLC patients progressing on, or intolerant to, crizotinib.

The global ALEX trial program is aimed at providing evidence for alectinib in the first-line NSCLC setting, for which Roche (which holds all rights outside Japan) made an approval filing in the EU last September, for ALK-positive unresectable, recurrent or advanced disease.

Datamonitor Healthcare sees Novartis AG's Zykadia (ceritinib) as Alecensa's main global competitor in both first- and second-line use, but said "the head-to-head design of Alecensa's Phase III trial in first-line patients will give it an advantage in this setting by encouraging uptake in place of Xalkori."

The Chugai drug is also more potent and has demonstrated efficacy against secondary mutations that can confer resistance to Xalkori and against the brain metastases that are common in ALK-positive NSCLC, Datamonitor notes.

Chugai booked Alecensa sales of JPY2.2bn ($20m; +69%) in the calendar first quarter and is expecting these to reach JPY9.6bn in the full year.

ASCO Preview: Alecensa Bests Xalkori In Japan Head-To-Head

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