Roche announced that Alecensa, an oral anaplastic lymphoma kinase (ALK) inhibitor, reduced the risk of disease worsening or death (progression free survival, PFS) by 66 per cent compared to crizotinib in Japanese people with advanced or recurrent, ALK-positive non-small cell lung cancer (NSCLC) (hazard ratio [HR]=0.34, 99 per cent CI: 0.17-0.70, p<0.0001). Median PFS was not reached in people who received Alecensa (95 per cent CI: 20.3 months-not reached) versus 10.2 months median PFS (95 per cent CI: 8.2-12.0) in people who received crizotinib.

The results were from a pre-specified interim analysis from the phase III J-ALEX study in people who had not received prior treatment with an ALK-inhibitor. There were fewer adverse events (AEs) in the Alecensa arm versus the crizotinib arm. Alecensa demonstrated a safety profile consistent with that observed in previous studies with no new or unexpected AEs.

“This is the first investigational study to show Alecensa helped people live longer without their disease getting worse compared to crizotinib,” said Sandra Horning, MD, chief medical officer and head of global product development. “We believe these efficacy and safety results represent a clinically meaningful advancement for people with ALK-positive lung cancer, and we plan to discuss these data with health authorities, including the FDA.”

The official J-ALEX data presentation at the American Society of Clinical Oncology (ASCO) annual meeting will be on Monday 6th June, from 12:09 - 12:21 CDT (Abstract #9008). The data will be featured during the Roche media briefing from 10:45 - 12:30 CDT on Friday 3rd June at the Chicago Marriott Hotel Downtown Magnificent Mile. This event, independently organised by Roche, is open to journalists from outside the United States who have registered as media with the ASCO 2016 Annual Meeting.

Alecensa was granted accelerated approval by the US Food and Drug Administration (FDA) in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. ALEX, a global, randomised phase III study, is ongoing, comparing Alecensa to crizotinib as an initial (first-line) treatment for people with advanced NSCLC whose tumours were characterised as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. This study is part of the company’s commitment to convert the current accelerated approval in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.

The J-ALEX study conducted by Chugai is an open-label, randomised phase III study that compared the efficacy and safety of Alecensa to crizotinib in Japanese people. The J-ALEX study enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been previously treated with an ALK-inhibitor. People were randomised to the Alecensa group or the crizotinib group in a one-to-one ratio.

Results include: Alecensa reduced the risk of disease worsening or death (PFS) by 66 per cent compared to crizotinib (HR=0.34, 99 per cent CI: 0.17-0.70, p<0.0001);    Median PFS was not reached in the Alecensa arm (95 per cent CI: 20.3 months-not estimated) versus 10.2 months in the crizotinib arm (95 per cent CI: 8.2-12.0);  Grade 3-4 AEs occurred with greater frequency in the crizotinib arm compared to the Alecensa arm (51 per cent vs. 27 per cent);  The most common AE occurring with > 30 per cent frequency with Alecensa was constipation (36 per cent). The most common AEs for crizotinib were nausea (74 per cent), diarrhoea (73 per cent), vomiting (59 per cent), visual disturbance (55 per cent), alteration in taste (dysgeusia; 52 per cent), constipation (46 per cent), and an elevation in liver enzymes called alanine transaminase (ALT, 32 per cent) and aspartate transaminase (AST, 31 per cent).

Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK+. ALK+ NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States for the treatment of advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In two key phase II studies, NP28761 and NP28673, Alecensa shrank tumours in up to 44 per cent of people with ALK-positive NSCLC who progressed on crizotinib. Alecensa also demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III studies of Alecensa include a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.