Boehringer Ingelheim submits nintedanib*, a novel oncology compound, for European approval

Nintedanib*, in combination with docetaxel, filed for second-line treatment of advanced non-small cell lung cancer (NSCLC) of adenocarcinoma histology after first line chemotherapy

•  Following recent approval of GIOTRIF® in NSCLC, Boehringer Ingelheim files its second oncology compound with European Medicines Agency

Boehringer Ingelheim announced the submission of a Marketing Authorisation Application to the European Medicines Agency for the approval of its oral triple angiokinase inhibitor nintedanib*, in combination with docetaxel, for the treatment of patients with locally advanced, metastatic or recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour histology after first line chemotherapy. Nintedanib*, when added to chemotherapy, is the first lung cancer treatment that extended patient survival beyond one year in a broad population of adenocarcinoma patients, after initial chemotherapy had failed.¹

“Improving patients’ lives remains at the forefront of Boehringer Ingelheim’s commitment to evidence based progress in the treatment of cancer.” said Prof Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. “We are proud that nintedanib*, a compound out of our innovative oncology research programme, is the second compound in our portfolio to be filed with the European Medicines Agency.”

Lung cancer causes more deaths than any other cancer and only approximately one out of six patients survive 5 years from diagnosis.² Adenocarcinoma is the most common type of lung cancer and more than two-thirds of patients are diagnosed at a late stage when curative treatment is no longer feasible. Ultimately, all patients with advanced adenocarcinoma will progress and require second-line treatment.³

The EU Marketing Authorization Application for the approval of nintedanib* is based on the international, double-blind, Phase III LUME-Lung 1 trial, which was the first trial to show a survival benefit of an add-on treatment in a broad second line adenocarcinoma patient population versus an active comparator (standard-of-care/chemotherapy). In this trial in advanced NSCLC patients, the combination of nintedanib* plus docetaxel demonstrated a statistically significant prolonged progression-free survival (PFS), versus placebo (3.4 vs. 2.7 months, respectively) regardless of tumour histology, reducing the risk of renewed tumour growth by 21%.¹

Overall survival was significantly prolonged in adenocarcinoma patients treated with nintedanib* plus docetaxel versus placebo plus docetaxel (12.6 vs. 10.3 months respectively).1 The results demonstrated that patients with adenocarcinoma who have failed initial treatment with chemotherapy received on average a 20% extension of overall survival. In addition, the data demonstrated that the earlier adenocarcinoma patients failed first line chemotherapy, the bigger the benefit nintedanib provided, as patients who progressed within 9 months (T<9 months) after start of their first-line treatment, achieved a median overall survival benefit of 3 months (10.9 vs. 7.9 months).⁴

The trial results showed patients benefitted from the additional efficacy of nintedanib* without further impacting their quality of life. The most common adverse events (AEs) in LUME-Lung 1 were gastrointestinal side effects and reversible liver enzyme elevations which were manageable by supportive treatment or dose reduction (adverse events nintedanib* vs. placebo: nausea 24% vs. 18%, vomiting 17% vs. 9%, diarrhoea 42% vs. 22%and liver enzyme elevation 29% vs. 8%). Withdrawal due to adverse events was similar in both arms, as were Grade 3, bleeding or thromboembolic events.¹

Nintedanib* is an oral triple angiokinase inhibitor which targets the three receptors crucially involved in angiogenesis and tumour growth.

Boehringer Ingelheim endeavours to make nintedanib* available to patients around the world. Further submissions worldwide are planned.

Notes to Editors

About the LUME-Lung 1 trial
LUME-Lung 1 is a randomised, double-blind, Phase III study comparing nintedanib* plus docetaxel in patients with locally advanced/metastatic NSCLC after first-line therapy, with placebo plus docetaxel. The study included 1,314 patients, in Europe, Asia and South Africa, randomised to receive nintedanib* 200 mg twice daily plus docetaxel 75mg/m2 once a day, for 3 weeks (n=655) or placebo plus docetaxel (n=659).

LUME-Lung 1 is part of the wider Boehringer Ingelheim LUME-Lung Phase III programme for nintedanib*, investigating the safety and efficacy of nintedanib* in NSCLC patients after first line chemotherapy treatment. 1,773 patients were enrolled, making this one of the largest Phase III study programmes in this NSCLC patient population to date.

About Nintedanib*
Nintedanib* is an oral triple angiokinase inhibitor that targets three growth factor receptors simultaneously: vascular endothelial growth factor receptors (VEGFR 1-3), platelet-derived growth factor receptors (PDGFR alpha and beta), and fibroblast growth factor receptors (FGFR 1-3).⁵ All three receptors are crucially involved in the formation and maintenance of new blood vessels (angiogenesis); their blockade may lead to the inhibition of angiogenesis, which plays a critical role in tumour growth and spread.^6,7

Nintedanib* is currently being investigated in patients with various solid tumours including advanced NSCLC, ovarian cancer, liver cancer (hepatic cell carcinoma), kidney cancer (renal cell carcinoma), and colorectal cancer.

About Lung Cancer
Lung cancer is one of the most common and most deadly forms of cancer in the world, it accounts for 1.6 million new cancer cases annually.⁸ Because of its poor prognosis, 1.38 million deaths each year are attributable to lung cancer.⁸ Overall, lung cancer is the cause of 18% of all cancer deaths.⁸ Approximately 228,190 (13%) of all new cases of cancer are lung cancers² and smoking is attributed as the main cause.

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: signal transduction inhibition, angiogenesis inhibition and cell-cycle kinase inhibition. In the EU, Taiwan and Mexico, afatinib is approved under the brand name GIOTRIF®, and in the U.S. under the brand name GILOTRIFTM for use in patients with distinct types of NSCLC. Afatinib is under regulatory review by health authorities in Asia and other countries. Nintedanib*, an angiogenesis inhibitor is currently in Phase III clinical development in NSCLC and ovarian cancer. In the area of cell-cycle kinase inhibition, volasertib* is in phase III development for acute myeloid leukaemia.

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

References

1. Reck M et al. Nintedanib (BIBF 1120) + docetaxel in NSCLC patients progressing after first line chemotherapy: LUME Lung 1, a randomized, double-blind phase 3 trial. Oral Presentation at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, USA 31 May – 4 June 2013.
2. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, 2013.
3. Cancer Research UK. CancerStats key facts on lung cancer and smoking. CancerStats – Key Facts 2009. [Online] Available at: http://info.cancerresearchuk.org/cancerstats/types/lung/ [Last Accessed April 2009].
4. Mellemgaard A et al. Analysis of overall survival in adenocarcinoma NSCLC patients receiving second-line combination treatment with nintedanib (BIBF 1120) + docetaxel in the LUME-Lung 1 trial: a randomised, double-blind, placebo-controlled phase III study. Oral Presentation at the European Cancer Congress 2013.
5. Hilberg F, Roth GJ, Krssak M,&nbsp; et al. BIBF1120: triple angiokinase inhibitor with sustained receptor blockade and good anti-tumor efficacy. Cancer Res 2008;68: 4774-82.
6. Folkman N. Clinical applications of research on angiogenesis. N Engl J Med 1995;333: 1757-63.
7. Bousquet C, Lamande N, Brand M, et al. Suppression of angiogenesis, tumor growth, and metastasis by adenovirus-mediated gene transfer of human angiotensinogen. Mol Ther 2006;14:175-82.
8. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.