Value through Innovation01 August 2014
20 September 2012

Boehringer Ingelheim submits first oncology compound, afatinib* for European approval

Boehringer Ingelheim’s compound afatinib* has been submitted for European approval for treatment of patients with EGFR (ErbB1) mutation positive non-small cell lung cancer.

Ingelheim, Germany, 20 September 2012 – Today, Boehringer Ingelheim has announced the submission of a Marketing Authorisation Application to the European Medicines Agency (EMA) for approval of afatinib*, the first irreversible ErbB Family Blocker, as a treatment for patients with EGFR (ErbB1) mutation positive non-small cell lung cancer (NSCLC). Afatinib* has demonstrated unprecedented efficacy versus chemotherapy in the Phase III LUX-Lung 3 registration trial, which provides pivotal support for this submission.1

NSCLC comprises over 85% of the 391,000 new cases of lung cancer diagnosed annually in Europe, with adenocarcinoma being the most common type of NSCLC.2-4 Approximately 20-30% of all lung adenocarcinomas harbour EGFR mutations.5-8 Because of its poor prognosis, approximately 340,000 deaths each year in Europe are attributed to lung cancer, making it the most common cause of cancer death.2

Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

"With so many people being diagnosed with, and dying from lung cancer, there is still a clear need for effective and tolerable therapies. Boehringer Ingelheim is committed to helping patients have access to afatinib* as soon as possible," said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The positive clinical evidence for afatinib*, coupled with its novel mode of action, could make this an outstanding treatment option, providing much needed benefits for lung cancer patients."

The submission is based on the comprehensive LUX-Lung clinical trial programme. Data from the pivotal LUX-Lung 3 trial, comparing afatinib* to the best-in-class chemotherapy (pemetrexed and cisplatin) for nonsquamous NSCLC, demonstrated superiority in patients with stage IIIb or IV adenocarcinoma of the lung harbouring an EGFR mutation. Patients taking afatinib* as a first-line treatment lived for almost one year without their tumour growing (progression-free survival (PFS) of 11.1 months) versus just over half a year (PFS of 6.9 months) for those on chemotherapy (pemetrexed / cisplatin).1 Furthermore, NSCLC patients with tumours harbouring the two most common EGFR mutations (del19 and L858R, accounting for 90% of all tumours with EGFR mutations) taking afatinib* lived for well over a year without disease progression (PFS of 13.6 months) versus just over half a year (PFS of 6.9 months) for those in the comparator arm.1

The delay in disease progression for afatinib*-treated patients was associated with an improvement of life-restricting lung cancer symptoms.9 More patients taking afatinib* experienced an improvement in dyspnoea (shortness of breath), cough, and chest pain. Afatinib* also significantly delayed the deterioration of these symptoms compared to chemotherapy.9

In addition, a standard questionnaire assessing the quality of life of lung cancer patients revealed that afatinib* treatment translated into a better quality of life (e.g. at work and during household activities).1

Additional data from the trial, including symptom improvement and health-related quality of life results, will be presented at the ESMO 2012 Congress (European Society for Medical Oncology) in Vienna, Austria, 28 September – 2 October 2012:

Title Lead Author
Session Details
LUX-Lung 3: Symptom and
health-related quality of life
results from a randomized
phase III study in 1st-line
advanced NSCLC patients
harbouring EGFR mutations
L. V. Sequist Poster Discussion Session: NSCLC,
metastatic
Poster number: 1229PD
Date: 30 September 2012
Time: 12:45 – 2:45 pm (CEST)

While the LUX-Lung 3 trial demonstrated the superiority of afatinib in delaying disease progression versus best-in-class chemotherapy (pemetrexed and cisplatin) for nonsquamous NSCLC, Boehringer Ingelheim is also exploring the broader potential of afatinib*. The company has initiated two head-to-head trials (LUX-Lung 7 and 8) directly comparing afatinib* to the currently available tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, respectively. Both trials are actively recruiting patients.

Notes to Editors

About Afatinib*

Afatinib* is the first irreversible ErbB Family Blocker which inhibits signal transduction of all kinase receptors from the ErbB Family10, which is known to play a critical role in the growth and spread of the most pervasive cancers and cancers associated with high mortality (lung, breast, and head & neck cancers). Afatinib* is currently also in Phase III clinical development in breast cancer and head & neck cancer.

About LUX-Lung 3 Trial
LUX-Lung 3 is the largest and most robust registration trial to date in patients with advanced EGFR mutation positive lung cancer. LUX-Lung 3 is a global, randomized, open-label, Phase III trial and the first to directly compare a tyrosine kinase inhibitor (afatinib*) to the standard chemotherapy agents, pemetrexed and cisplatin. The study included 345 previously untreated patients with EGFR mutation positive NSCLC.1

The most common drug-related adverse events observed in the afatinib* treatment arm were diarrhoea (95%), rash/acne (89%), and mucositis/stomatitis (72%). The most common drug-related adverse events observed in the chemotherapy arm (pemetrexed /cisplatin) were nausea (66%), decreased appetite (53%), and vomiting (42%). There was a low discontinuation rate associated with treatment-related adverse events in the trial (8% discontinuation rate for afatinib; 12% for chemotherapy). One percent of patients in the afatinib* arm discontinued treatment due to diarrhoea.

About Lung Cancer
Lung cancer is the most common and most deadly form of cancer in the world.4 In Europe, it accounts for 391,000 new cancer cases annually, and 342,000 deaths each year.2 Overall, lung cancer is the cause of 19.9% of all cancer deaths in Europe.2 Thirteen percent of all new cases of cancer are lung cancers11 and smoking is attributed as the main cause.12

Early testing for tumour EGFR mutation status of lung cancer patients is critical in improving patient outcomes. Between 10-15% of Caucasian and 40% of Asian NSCLC patients have tumours harbouring EGFR mutations, with 90% of these accounting for two mutations (del19 or L858R).13

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 programme 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. Nintedanib*, an angiogenesis inhibitor is currently in Phase III clinical development in NSCLC and ovarian cancer. In the area of cell-cycle kinase inhibition, Boehringer Ingelheim is developing an inhibitor of polo-like kinase 1 (Plk1), volasertib*, a protein that is involved in the processes of cell division. The compound is in Phase II development for acute myeloid leukaemia.

Boehringer Ingelheim’s oncology pipeline is evolving and demonstrates the company’s continued commitment to advance the disease area.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 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 endeavours.

In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

For more information please visit:www.boehringer-ingelheim.com and www.thewhiteroom.info

*Afatinib, nintedanib and volasertib are investigational compounds. Their safety and efficacy have not yet been fully established.

References

1. Abstract no: LBA7500, LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. Oral Presentation at 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) 2012.
2. Ferlay J et al. Estimates of cancer incidence and mortality in Europe in 2008. EJC 2010; 46 765-781.
3. Surveillance Epidemiology and End Results. Available at: http://www.seer.cancer.gov/csr/1975_2008/browse_csr.php?section=15&page=sect_15_table.28.htm. [Last Accessed August 2012].
4. Ferlay J et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127 2893-2917.
5. Non-Small Cell Lung Cancer Treatment (PDQ®). Cellular classification of NSCLC. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/healthprofessional/page2. [Last Accessed January 18, 2012].
6. Kris MG et al. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: the NCI’s Lung Cancer Mutation Consortium (LCMC). Abstract CRA7506. J Clin Oncol. 2011;29(June 20 suppl). http://meeting.ascopubs.org/cgi/content/abstract/29/18_suppl/CRA7506?sid=84701cef-e846-4865 9c01-bfdd7afe5871. [Last Accessed December 29, 2011].
7. Billah S, et al. EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol. 2011;119(2):111-117.
8. Pao W et al. Integration of molecular profiling into the lung cancer clinic. Clin Cancer Res. 2009;15(17):5317-5322
9. Abtract no: 2067. Sequist L. V. et al. LUX-Lung 3: Symptom and health-related quality of life results from a randomized phase III study in 1st-line advanced NSCLC patients harbouring EGFR mutations. ESMO 2012 Congress. Available at: http://abstracts.webges.com/myitinerary/session-148.html?congress=esmo2012#.UFdGtBr1LSY.gmail
10. Solca, F. et al. Target Binding Properties and Cellular Activity of Afatinib (BIBW 2992), an Irreversible ErbB Family Blocker (Fast Forward 10 August 2012) . J Pharmacol Exp Ther 2012 343 (2).
11. Cancer Research UK. UK lung cancer incidence. CancerStats – Key Facts 2009. [Online] Available at: http://info.cancerresearchuk.org/cancerstats/types/lung/incidence/ [Last Accessed July 2012].
12. Allen J et al. J Natl Compr Canc Netw 2008;6(3): 285-293.
13. Quest Diagnostics – Lung Cancer Mutation Panel. [Online] Available at: http://www.questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=TS_LungCancerMutation_Panel.htm [Last Accessed July 2012].

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