Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today 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. The FDA will make a decision on approval by November 30, 2017.

“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.”

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). 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.

About Roche in lung cancer

Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have four approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. 
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry eight years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.


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References:
1. Shaw AT, et al. Alectinib versus crizotinib in treatment-naïve advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study. Presented at: ASCO Annual Meeting; 2017 Jun 2-6; Chicago, IL, USA. Abstract #LBA9008. 
2. FDA. FDA approves new oral therapy to treat ALK-positive lung cancer. [Internet; cited 2017 May 22]. Available from: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm476926.htm. 
3. Takiguchi, et al. Updated efficacy and safety of the J-ALEX study comparing alectinib (ALC) with crizotinib 
CRZ) in ALK-inhibitor naive ALK fusion positive non small cell lung cancer (ALK+ NSCLC). Journal of Clinical Oncology. Presented at: ASCO Annual Meeting; 2017 Jun 2-6; Chicago, IL, USA. Abstract #9064.
4. ClinicalTrials.gov. A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants (ALEX) [Internet; cited 2017 June]. Available from: https://clinicaltrials.gov/ct2/show/NCT02075840.
5. Gridelli C, et al. ALK inhibitors in the treatment of advanced NSCLC. Cancer Treatment Reviews. 2014;40:300-306.

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