New treatment option for Canadians with metastatic lung cancer

Takeda Canada receives approval for ALUNBRIG™ for the treatment of adults with ALK+ metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to an ALK inhibitor (crizotinib)

OAKVILLE, ON, July 30, 2018 /CNW/ - Takeda Canada has received Notice of Compliance with conditions (NOC/c) approval from Health Canada for ALUNBRIG™ (brigatinib) indicated as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC) who have progressed on or who were intolerant to an ALK inhibitor (crizotinib).ⁱ ALUNBRIG™ is a new ALK inhibitor that meets the needs of patients with advanced lung cancer who urgently require more alternatives to the standard of care – crizotinib – because they are intolerant or the medicine has stopped working to slow the progression of this devastating, terminal disease.

NSCLC is the most common form of lung cancer, accounting for approximately 85 per cent of lung cancers diagnosed each year in Canada.ⁱⁱ ALK+ NSCLC is a subset of the disease, often striking people at a younger age, many of whom have never smoked or were light smokers.ⁱⁱⁱ

The central nervous system is a common site for this type of cancer to spread, even with initial treatment. Brain metastases is present in up to 70 per cent of patients after treatment with crizotinib.^iv Once cancer has spread to the brain, the median length of survival significantly decreases.^v

"New ALK inhibitors are needed that can help address resistance to crizotinib," said Dr. Geoffrey Liu, Senior Scientist, Princess Margaret Cancer Centre. "That's why the approval of ALUNBRIG™ is so important. People living with this type of cancer need new targeted treatments that will help slow down or halt tumour growth, and reduce brain metastases."

The ALTA (ALK in Lung Cancer Trial of AP26113) trial demonstrated clinically meaningful efficacy, with the majority of patients who received the recommended dosage achieving an objective response rate (ORR) and median progression free survival of greater than one year. The study also showed an intracranial ORR in the majority of patients with measurable brain metastases.^iv

"The approval of brigatinib is welcome news to the lung cancer community," said Shem Singh, Executive Director, Lung Cancer Canada. "Lung cancer remains the leading cause of cancer death in Canada. New treatments give patients more hope in the fight against this disease as researchers continue to work towards a cure."

ALUNBRIG™ works by targeting and blocking receptors found on the cancer cells called an anaplastic lymphoma kinase. In some cancers, this receptor is overactive, causing cells to grow and divide too fast. By inhibiting ALK, this medication may slow or stop cell growth of cancer cells tumour growth.[vi] Following the U.S. Food and Drug Administration priority review approval in April 2017, Canada is the second country in the world to approve ALUNBRIG™.

"Health Canada's approval of ALUNBRIG™ further reinforces Takeda's ongoing commitment to developing innovative therapies for people living with cancer and the healthcare professionals who treat them," says Gamze Yüceland, General Manager of Takeda Canada Inc. "We are proud to be the second country in the world to gain approval of ALUNBRIG™ as a critical treatment option for advanced lung cancer patients.

About the ALTA Trial

Health Canada's approval of ALUNBRIG™ was primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of brigatinib in adults. This ongoing, two-arm, open-label, multicenter trial enrolled 222 patients with metastatic ALK+ NSCLC who had progressed on crizotinib.^iv

With a median follow-up of 17.9 months, results demonstrated that of the patients who received the recommended dosing regimen (90→180 mg), 55.5 per cent achieved a confirmed ORR as assessed by the investigator and 54.5 per cent as assessed by an independent review committee (IRC); the median DOR was 13.8 months (investigator-assessed) and 14.8 months (IRC-assessed); PFS was 15.6 months (investigator-assessed) 16.7 months (IRC-assessed); and 66.7 percent of patients with measurable brain metastases (n=18), achieved a confirmed intracranial ORR (IRC-assessed).ⁱ

At the recommended dosing regimen, the most common adverse reactions reported in patients (≥10%) treated with ALUNBRIG™ at the 180 mg recommended regimen were nausea, diarrhea, fatigue, cough, headache, rash, vomiting, hypertension, dyspnea, myalgia, decreased appetite, muscle spasms, constipation, peripheral neuropathy, arthralgia, visual disturbances, abdominal pain, dizziness, edema and ILD/pneumonitis.ⁱ

The ALTA clinical development program further reinforces Takeda's ongoing commitment to developing innovative therapies for people living with ALK+ NSCLC worldwide and the healthcare professionals who treat them.^iv

About ALUNBRIG™ (brigatinib)

ALUNBRIG™ is an ALK inhibitor. It is a targeted medicine that blocks the action of the altered ALK gene to help shrink or slow cancer growth. ALUNBRIG™ is approved for the treatment of adults with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinibⁱ.

ALUNBRIG™ is administered orally, beginning with seven days of 90 mg once daily, followed by 180 mg once daily thereafter. ALUNBRIG™ received a priority approval in the U.S. and has also received accelerated approval by the U.S. FDA in April 2017. ALUNBRIG™ is currently under review by the European Medicines Agency (EMA).

ALUNBRIG™ is also being studied in the Phase 3 ALTA 1L trial to assess its efficacy and safety in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor.

ALUNBRIG™ is a trademark of ARIAD Pharmaceuticals, Inc. and used under licence by Takeda Canada Inc.

About ALK+ Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent^vii of lung cancer cases diagnosed each year in the Canada, according to the Canadian Cancer Society. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Between three to five per cent of NSCLC tumours are ALK-positive.^viii

About Takeda

Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda's presence in emerging markets, are currently fueling the growth of Takeda. Around 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda's partners in health care in more than 70 countries. For more information, visit https://www.takeda.com/newsroom/.

Takeda Canada, located in Oakville, Ontario, is the Canadian sales and marketing organization of Takeda Pharmaceutical Company Limited. Takeda Canada is delivering better health for Canadians through leading innovations in gastroenterology and oncology. Additional information about Takeda Canada is available at takeda.com/en-ca.

REFERENCES

^i ALUNBRIG™ Product Monograph. Takeda Canada Inc. July 25, 2018
^iiCanadian Cancer Statistics 2015
^iiCanadian Cancer Society. Malignant tumours of the lung. Available at http://www.cancer.ca/en/cancer- information/cancer-type/lung/lung-cancer/cancerous-tumours/?region=on. Accessed on February 2018.
^iii Gridelli, et al. ALK inhibitors in the treatment of advanced NSCLC. Cancer Treat Rev 2014;40(2): 300–306.
^ivA. Wong. The Emerging Role of Targeted Therapy and Immunotherapy in the Management of Brain Metastases in Non- Small Cell Lung Cancer Front Oncol. 2017; 7: 33. Published online 2017 Apr 5. doi:  10.3389/fonc.2017.00033. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380676/. Accessed February 2018
^v Ray et al. Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer. Journal of Neuro-Oncology. 2013 May. Available online at:https://www.researchgate.net/publication/236934231_Comparative_analysis_of_survival_treatment_cost_and_reso urce_use_among_patients_newly_diagnosed_with_brain_metastasis_by_initial_primary_cancer Last accessed on February 2018.
^vi OncoLink. Brigatinib (Alunbrig™). Available at: https://www.oncolink.org/cancer-treatment/chemotherapy/oncolink- rx/brigatinib-alunbrig Accessed: February 2018
^vii Canadian Cancer Society. Malignant tumours of the lung. Available at http://www.cancer.ca/en/cancer- information/cancer-type/lung/lung-cancer/cancerous-tumours/?region=on. Accessed February 2018.
^viii Gainor JF, Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013; 19(15):4273-81.

SOURCE Takeda Canada Inc.

Media contact: Natacha Raphael, Corporate Communications, Takeda Canada Inc., Tel: [phone], [email protected]