Roche has announced that the European Union’s (EU) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Alecensa (alectinib) as a monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC). It has also simultaneously recommended the conversion of the current conditional marketing authorisation for Alecensa in crizotinib failure (second-line) to a full marketing authorisation.

The CHMP recommendation in first-line is based on results from the global phase III ALEX study, which showed Alecensa significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 53% (HR=0.47, 95% CI: 0.34-0.65, p<0.001) compared with crizotinib. The study also showed that Alecensa reduced the risk of tumours spreading to, or growing in, the brain or central nervous system (CNS) by 84% (HR=0.16, 95% CI: 0.10-0.28, p<0.001), compared with crizotinib. The safety and tolerability profile of Alecensa compared favourably to that of crizotinib despite the longer duration of treatment with Alecensa (17.9 vs. 10.7 months), and was consistent with that observed in previous studies.

“This is more great news for people with this type of lung cancer, bringing them closer to benefiting from Alecensa’s superior efficacy earlier in their treatment journey,” said Sandra Horning, MD, Roche’s chief medical officer and head of Global Product Development. “The results from ALEX clearly showed the significant benefits of Alecensa over crizotinib and we are pleased this has been recognised by the CHMP.”

The next step would be for the European Commission to make its final decision. A positive decision would mean approval for Alecensa across both the first-line and crizotinib failure settings in Europe. Alecensa was recently granted Priority Review by the US Food and Drug Administration (FDA) in the first-line setting in the United States, and has been approved in the crizotinib failure setting since 2015.

ALEX (NCT02075840/B028984) is a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study is PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (as defined by RECIST criteria), duration of response, overall survival, health-related quality of life and safety. The multicentre study was conducted in 303 people across 161 sites in 31 countries.

Alecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive 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, Europe, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Australia, Singapore, Taiwan, Thailand, Liechtenstein, Argentina, United Arab Emirates, Saudi Arabia and Turkey for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib and in Japan for people with ALK-positive NSCLC.