On August 3, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) and granted Priority Review for Alecensa (alectinib) as an initial (first-line) treatment for people with anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test (Press release, Hoffmann-La Roche, AUG 2, 2017, View Source [SID1234520002]). The FDA will make a decision on approval by November 30, 2017. Schedule your 30 min Free 1stOncology Demo! "Phase III results showed Alecensa reduced the risk of disease worsening by more than half compared to the current standard of care and lowered the risk of tumours spreading to or growing in the brain by more than 80%,"1 said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are working closely with the FDA to bring this medicine as an initial treatment for people with ALK-positive NSCLC as soon as possible."
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
This sNDA submission for Alecensa is based on results from the phase III ALEX and phase III J-ALEX studies. A Priority Review designation is granted to proposed medicines that, if approved, the FDA has determined to have the potential to provide a significant improvement in the safety or effectiveness of the treatment, prevention or diagnosis of a serious disease.
In addition, on March 25, 2017, the European Medicines Agency (EMA) validated the extension of indication application for Alecensa as an initial treatment for people with this specific form of lung cancer. This submission was also based on the pivotal phase III ALEX and J-ALEX studies.
Alecensa received Breakthrough Therapy designation from the FDA in September 2016 for the treatment of adults with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. Breakthrough Therapy designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. Breakthrough Therapy designation was granted on the basis of the phase III J-ALEX trial.
Alecensa was granted accelerated approval by the FDA in December 2015 for the treatment of people with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.2 The ALEX study is part of the company’s commitment in the US to convert the current accelerated approval of Alecensa in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.
About the ALEX and J-ALEX studies1,3
Results from the phase III ALEX study and updated results from the phase III J-ALEX study were recently presented at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). 1,3
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 (one-to-one ratio) to receive either Alecensa or crizotinib. The multicentre study was conducted in 303 people across 161 sites in 31 countries.4 Results include:1
Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 53% compared to crizotinib (hazard ratio [HR]=0.47, 95% CI: 0.34–0.65, p<0.0001).
Investigator-reported median PFS (the primary endpoint) was not yet reached in the Alecensa arm (95% CI: 17.7–not reached) versus 11.1 months (95% CI: 9.1–13.1 months) in the crizotinib arm.
Independent Review Committee (IRC)-reported median PFS (a secondary endpoint) was 25.7 months (95% CI: 19.9–not reached) in the Alecensa arm versus 10.4 months (95% CI: 7.7–14.6 months) in the crizotinib arm (HR=0.50, 95% CI: 0.36–0.70, p<0.0001).
Alecensa reduced the risk of progression in the central nervous system (CNS) by 84% (HR=0.16, 95% CI: 0.10–0.28, p<0.0001) versus crizotinib.
The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4% (95% CI: 5.4%–14.7%) for people treated with Alecensa and 41.4 % (95% CI: 33.2%–49.4%) for people treated with crizotinib.
Overall survival (OS) data are currently considered immature with only about a quarter of events being reported.
Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (41%) compared to the crizotinib arm (50%). In the Alecensa arm, the most common Grade 3–5 AEs (≥5%) were increased liver enzymes (alanine transferase and aspartate transferase; 5%) and decreased red blood cells (anaemia; 5%). AEs leading to discontinuation (11% vs. 13%), dose reduction (16% vs. 21%) and dose interruption (19% vs. 25%) were all lower in the Alecensa arm compared to the crizotinib arm.
The J-ALEX study is an open-label, randomised phase III study conducted by Chugai that compared the efficacy and safety of Alecensa with crizotinib in Japanese people. J-ALEX enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been treated with an ALK inhibitor. People were randomised to the Alecensa group or the crizotinib group on a one-to-one ratio.3 Results include:3
Alecensa reduced the risk of disease worsening or death (PFS) by 62% compared to crizotinib (HR=0.38, 95% CI: 0.26–0.55, p<0.0001).
The median PFS was 25.9 months in the Alecensa arm (95% CI: 20.3–not reached) versus 10.2 months (95% CI: 8.3–12.0 months) in the crizotinib arm.
Alecensa reduced the risk of progression in the CNS by 81% (HR=0.19, 95% CI: 0.07-0.53) in people without brain metastases at baseline, and reduced the risk of CNS progression by 49% (HR=0.51, 95% CI: 0.16-1.64) in people with brain metastases at baseline.
Grade 3–4 adverse events (AEs) were less frequent in the Alecensa arm (32%) compared to the crizotinib arm (57%). In the Alecensa arm, the most common grade 3–4 AEs (≥5%) were an increase in muscle enzymes (blood creatine phosphokinase increase; 5%) and interstitial lung disease (5%). AEs leading to discontinuation (11% vs. 23%) and dose interruption (29% vs. 64%) were lower in the Alecensa arm compared to the crizotinib arm.
About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai 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.5 It is almost always found in people with a specific type of NSCLC called adenocarcinoma.5 Alecensa is currently approved in the United States, Europe, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Australia, Singapore and Taiwan for the treatment of 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.
The global phase III ALEX study of Alecensa includes a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.