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

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

“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:

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.

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.

*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.
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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].
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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].
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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].