The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Roche's alectinib for the treatment of people living with non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase fusion gene-positive (ALK+).

The approval was based on results from a Japanese phase I/II clinical study (AF-001JP) for people whose tumours were advanced, recurrent or could not be removed completely through surgery (unresectable).

“The approval of alectinib, a treatment specifically targeted to ALK+ lung cancer, in Japan is great news for people living with this difficult to treat disease,” said Sandra Horning MD, Roche’s chief medical officer and ead of global product development. “Another interesting aspect of alectinib is that based on early studies it may also work in people living with tumours that have spread to the brain, a difficult area to reach with current medicines. Our research will continue in this area."

Alectinib is expected to be made available in Japan later this year. Alectinib was also granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (US FDA) in June 2013 for patients with ALK+ NSCLC who progressed on crizotinib. BTD is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.

Global pivotal studies are currently ongoing which will further inform on the clinical value of alectinib in this disease setting as well as in treatment-naïve patients. The results of these studies will be used in future regulatory submissions in the US and in Europe.

This trial was conducted in 13 medical institutions in ALK fusion gene positive recurrent or advanced non-small cell lung cancer patients with a treatment history of one or more chemotherapy regimens.

The trial consisted of two phases: Phase I that evaluated safety, tolerability, pharmacokinetic parameters and recommended dose (24 patients), and a Phase II part that evaluated the efficacy and safety of the recommended dose (46 patients). The primary endpoint was response rate.

Japanese Phase I/II study (AF-001JP) results. The Phase I part of the study determined a recommended dose of 300 mg twice daily. No dose limiting toxicity was observed.

The Phase II portion of the study was conducted using the recommended dose, and demonstrated a response rate of 93.5% (43/46 patients; 95%CI: 82.1-98.6%). 14 patients entered the study with Central Nervous System (CNS) metastases. 9 of the 14 patients remained in the study without CNS or systemic progression for more than 12 months.

There were no treatment-related deaths and/or grade 4 or higher serious adverse reactions assessed according to CTCAE (Common Terminology Criteria for Adverse Events) defined by the Japan Clinical Oncology Group. The most frequently observed grade 3 or higher adverse reaction was neutropenia, and the incidence of the adverse event was 4 out of 58 patients (6.9%) who were treated with 300 mg twice daily, the approved dose.

Alectinib (RG7853/AF-802/RO5424802/CH5424802) is an investigational 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, women and those who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC, 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 3 studies2 of alectinib include a companion test co-developed with Ventana Medical Systems, Inc., a member of the Roche Group. Alectinib will be marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

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.