Investor Update

Basel, 09 September 2015

FDA grants Roche's alectinib Priority Review for specific type of ALK-positive lung cancer

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) and granted Priority Review for alectinib (known as Alecensa in Japan and the U.S.), an oral investigational anaplastic lymphoma kinase (ALK) inhibitor, for the treatment of people with ALK-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. Alectinib was granted Breakthrough Therapy Designation by the FDA in June 2013 for people with ALK-positive NSCLC whose disease progressed on crizotinib.

“Alectinib was granted Priority Review by the FDA based on results from two studies showing the medicine shrank tumours in people with ALK-positive NSCLC that progressed on crizotinib,” said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “There is a need for new treatment options in this patient population, especially because the disease often spreads to the brain at progression.”

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. 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. The NDA for alectinib includes data from two Phase II studies (NP28761 and NP28673), and the FDA will make a decision on approval by 4 March 2016.

ALEX, an ongoing, global randomised Phase III study is comparing alectinib to crizotinib as an initial (first-line) treatment for people with advanced NSCLC whose tumours were characterised as ALK-positive by a companion immunohistochemistry (IHC) test developed by Roche Diagnostics.

About the NP28761 and NP28673 Studies

Results from the Phase II NP28761 and NP28673 studies were recently presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO).

  • NP28761 is a North American, single-arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib.
    - Response assessment by an independent review committee (IRC) showed that alectinib shrank tumours (objective response rate, ORR) in 47.8% (95% confidence interval [CI] 35.6%-60.2%) of people treated with alectinib, as measured by Response Evaluation Criteria in Solid Tumours (RECIST v1.1).
    - Investigator assessment showed that alectinib shrank tumours in this group of people with a similar response rate (ORR of 46.0%, [95% CI 35.2%-57.0%]).
    - Activity was also observed in the central nervous system (CNS), as shown by a CNS ORR by IRC of 68.8% (95% CI 41.3%-89.0%) in people whose disease had already spread to the brain or other parts of the CNS at study entry.
    - People whose tumours shrank in response to alectinib continued to respond for a median of 7.5 months (duration of response [DOR], immature data).
    - The immature median progression-free survival (PFS) was 6.3 months (95% CI 5.5 months–not estimable) based on 40% of events.
  • In study NP28761, alectinib demonstrated a safety profile consistent with that observed in previous studies.
    - The most common Grade 3 or higher adverse events were increased muscle enzymes (increased blood levels of creatine phosphokinase; 8%), increased liver enzymes (alanine aminotransferase; 6%, and aspartate aminotransferase; 5%) and shortness of breath (dyspnea; 3%).
  • NP28673 is a global, single-arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib.
    - An IRC analysis showed that alectinib shrank tumours (ORR of 50.0%, [95% CI 40.8%-59.1%]) in this group of people, as measured by RECIST.
    - Assessment by investigator was consistent with the IRC and also showed that alectinib shrank tumours in this group of people (ORR of 47.8%, [95% CI 39.3%-56.5%]).
    - Activity was also observed in the CNS, as shown by a CNS ORR by IRC of 57.1% (95% CI 39.4%-73.7%) in people whose disease had already spread to the brain or other parts of the CNS at study entry.
    - People who achieved a response continued to respond for a median of 11.2 months (DOR, immature data based on 33% of events, [95% CI 9.6 months-not estimable]).
    - The median PFS for people who received alectinib was 8.9 months (95% CI 5.6 months-11.3 months) based on 58% of events.
  • Alectinib demonstrated a safety profile in study NP28673 consistent with that observed in previous studies.
    - The most common Grade 3 or higher adverse event was shortness of breath (dyspnea; 4%).

About alectinib

Alectinib (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura Research Laboratories for certain 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. The people whose NSCLC is ALK-positive almost always have adenocarcinoma.

Early studies with alectinib have shown activity on 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 alectinib, which means that it may travel into and throughout brain tissue.

The Global Phase III studies of alectinib include a companion test developed by Roche Diagnostics. Alectinib 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 two approved medicines to treat certain kinds of lung cancer and more than 10 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

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. 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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