GIOTRIF® (afatinib) Approved by Health Canada as a Treatment for Patients With Metastatic Adenocarcinoma of the Lung With Activating EGFR Mutation(s) Who Are Tyrosine Kinase Inhibitor Naive

GIOTRIF® (afatinib) Approved by Health Canada as a Treatment for Patients With Metastatic Adenocarcinoma of the Lung With Activating EGFR Mutation(s) Who Are Tyrosine Kinase Inhibitor Naive

BURLINGTON, ON, Nov. 7, 2013 /CNW/ - Boehringer Ingelheim (Canada) Ltd. announced today that Health Canada has approved GIOTRIF^® (afatinib) tablets for oral use, as a new treatment for Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor naïve patients with metastatic (including cytologically proven pleural effusion) adenocarcinoma of the lung with activating EGFR mutation(s).ⁱⁱ Approximately 20 per cent of all lung cancer cases have reported EGFR mutations.ⁱⁱⁱ

"The approval of GIOTRIF^® is an exciting advancement because it works differently than other drugs in its class, by irreversibly blocking multiple EGFR pathways involved in tumour growth," says Dr. Vera Hirsh, medical oncologist in the Department of Medical Oncology at Royal Victoria Hospital in Montreal, Associate Professor at McGill University and GIOTRIF^® clinical trial investigator. "This gives patients with EGFR mutation positive NSCLC a new option to fight their disease in a personalized way, according to the tumour's characteristics, allowing them to live without progression of their disease and also deterioration of their symptoms."

EGFR mutation positive NSCLC is one of many different types of lung cancer. NSCLC accounts for more than 85 per cent of all lung cancer diagnoses.^iv Among patients diagnosed with NSCLC, it is estimated that between 10 and 15 per cent of Caucasians and approximately 40 per cent of Asians have EGFR mutations.^v We also know the face of the disease is changing. People who never smoked, women and East Asians are at a higher risk for the EGFR genetic mutation.ⁱⁱⁱ

"There has been major progress in the fight against lung cancer in Canada. We have learned that there are many different types of lung cancer, each requiring a unique approach to treatment," says Mr. Shem Singh, Executive Director of Lung Cancer Canada. "It's critical that Canadians with lung cancer have access to gene testing for their cancer - this gene testing plays a key role in getting the right treatment to the right person for the best possible outcome, specifically targeting the genetic make-up of their lung cancer."

In clinical trials, GIOTRIF^® has been shown to offer patients with EGFR mutation positive NSCLC a significant delay in tumour progression,ⁱ coupled with improvements in their lung cancer related symptoms (such as shortness of breath and cough).ⁱ

The most common treatment related adverse events were diarrhea, rash/acne, and stomatitis for GIOTRIF^® and nausea, fatigue, and decreased appetite for chemotherapy.^vi

Ruth Wasylenko knows first-hand the impact lung cancer can have and the importance of new treatment options. Ms. Wasylenko is a non-smoker with lung cancer who has been taking GIOTRIF^®. "Lung cancer is a very aggressive disease and it can be devastating," says Ms. Wasylenko, a 60-year old priest who lives in Edmonton. "It's important that other lung cancer patients like me get access to new, effective treatments, so they too can get the best defense against their disease."

Lung cancer is the number one cancer killer in Canada, taking more lives than from colorectal, breast and prostate cancer combined.^vii One in every 11 Canadians will develop lung cancer during his or her lifetime.^viii The estimated 5-year survival rate for lung cancer is just 17 per cent.^vi This lags far behind that of other major cancers.^vi

"The approval of GIOTRIF^® in Canada reinforces Boehringer Ingelheim's commitment to researching and developing new therapies that may help extend the overall survival and quality of life for Canadians living with cancer," says Dr. Ted Witek, President and CEO from Boehringer Ingelheim (Canada) Ltd. "Over the past decade, great strides have been made in understanding the biology of lung cancer and GIOTRIF^® marks the first of what we expect will be many oncology products to emerge from our research and development program."

Discovered and developed by Boehringer Ingelheim, GIOTRIF^® is the first Health Canada-approved oncology product from the company.

About the LUX-Lung Clinical Trial Program

The approval of GIOTRIF^® was based on data from the LUX Lung 2 and the pivotal LUX-Lung 3 trial.

The LUX-Lung 2 trial shows that GIOTRIF^® is active in the treatment of patients with advanced lung adenocarcinoma EGFR mutations, irrespective of previous chemotherapy exposure, with a positive benefit / risk ratio.

Of the two most common adverse events (diarrhea and rash or acne), grade 3 events were more common in patients receiving a 50 mg starting dose (22 [22%] of 99 patients for diarrhea and 28 [28%] of 99 patients for rash or acne) than they were in those receiving a 40 mg starting dose (two [7%] of 30 patients for both diarrhea and rash or acne); possibly treatment-related serious adverse events were also less common in patients receiving a 40 mg starting dose (two of 30 patients vs 14 of 99 patients). ^ix

The LUX-Lung 3 trial is one of the largest Phase III trials conducted to date in the first-line EGFR mutation-positive, locally advanced or metastatic NSCLC treatment setting. Data from this trialshowed that patients taking GIOTRIF^® as a first-line treatment lived for almost one year without their tumour growing again (median progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those treated with the chemotherapy arm (pemetrexed/cisplatin) (p<0.001). In addition, a subgroup analysis showed that NSCLC patients with tumours harbouring the two most common EGFR mutations (Del 19 or L858R) taking GIOTRIF^® lived for well over a year without tumour progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.ⁱ

In the LUX-Lung 3 trial, the most common drug-related adverse events with GIOTRIF^® were diarrhea (96%), rash/dermatitis acneiform (90%), stomatitis (71%), paronychia (58%), dry skin (31%), decreased appetite (29%) and pruritus (21%). Serious adverse events (SAEs) were reported in 29 per cent of patients treated with GIOTRIF^®; the most frequent SAEs were diarrhea (6.6%); vomiting (4.8%); and dyspnea, fatigue, and hypokalemia (1.7% each).ⁱ

About GIOTRIF^® (afatinib)
GIOTRIF^® is a targeted monotherapy for the treatment of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor naïve patients with metastatic (including cytologically proven pleural effusion) adenocarcinoma of the lung with activating EGFR mutation(s).ⁱⁱ GIOTRIF^®'s unique mode of action enables it to block EGFR (ErbB1) as well as the other relevant members of the ErbB Family that are known to play a critical role in the growth and spread of the most pervasive cancers and cancers associated with high mortality. The covalent and, therefore, irreversible binding of GIOTRIF^® is unlike other compounds which are reversible in that it provides a sustained, selective, and complete ErbB Family Blockade.^{x, xi}

About Boehringer Ingelheim in Oncology
Building on scientific expertise and excellence in the fields of pulmonary and cardiovascular medicine, metabolic disease, neurology, virology and immunology, Boehringer Ingelheim has embarked on a major research program to develop innovative cancer drugs. Working in close collaboration with the international scientific community and a number of the world's leading cancer centres, Boehringer Ingelheim's commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumours and haematological cancers.

The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. Boehringer Ingelheim's oncology pipeline is evolving and demonstrates the company's continued commitment to advance the disease area.

About Boehringer Ingelheim (Canada) Ltd.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in its Prescription Medicines business corresponds to 22.5% of its net sales.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs more than 550 people across Canada. For more information please visit www.boehringer-ingelheim.ca.

References _______________________
i	Sequist, Lecia V. et al. "Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations." Journal of Clinical Oncology. 31.27 (2013): 3327-3334.
ii	GIOTRIF® Canadian Product Monograph. Page 3.
iii	Pao W, Miller VA. Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol 2005;23:2556-2568, Page 2561.
iv	Torok, Szilvia, et al. "Lung cancer in never smokers." Future Oncology. 7.10 (2011): 1196
v	L.W., Brady, Heilmann H.p, Molls M., and Neider C.Advances in Radiation Oncology in Lung Cancer. Second. Berlin: Springer-Verlag, 2011. Print.
vi	Sequist, Lecia V. et al. "Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations." Journal of Clinical Oncology. 31.27 (2013): 3327-3334.
vii	Canadian Cancer Society's Advisory Committee on Canadian Cancer Statistics. Canadian Cancer Statistics 2013 Page Page 43
viii	Canadian Cancer Society's Steering Committee: Canadian Cancer Statistics 2013. Toronto,ON: Canadian Cancer Society; 2012, Page 21.
ix	Yang, James, et al. "Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncology. 13.5 (2012): 539-548.
x	Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther 2012;343:342-50.
xi	Reid A, Vidal L, Shaw H, do Bono J. Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). Eur J Cancer 2007;43:481-9.

SOURCE Boehringer Ingelheim (Canada) Ltd.