Anti-Cancer Drug Closer to Marketplace

Boehringer Ingelheim (Ingelheim, Germany) announced on September 20, 2012, the submission of a marketing authorization application (MAA) to the European Medicines Agency (EMA) for the approval of afatinib. If approved, Afatinib will be a significant competitor to currently available EGFR tyrosine kinase inhibitors Tarceva and Iressa. What differentiates afatinib is that it is an irreversible ErbB family inhibitor of EGFR (ErbB1), HER2, ErbB2, and ErbB4, whereas Tarceva and Iressa are reversible inhibitors that target EGFR only.

The findings of LUX-Lung 3 trial, a global, randomized, open-label, phase III trial, provide pivotal support for this MAA submission. Afatinib demonstrated strong efficacy versus standard chemotherapy agents, Eli Lilly’s (Indianapolis, IN, USA) Alimta (pemetrexed) and cisplatin. The study included 345 previously untreated patients with EGFR mutation positive NSCLC, and patients who received afatinib as a first-line treatment lived for nearly one year without their tumor growing (progression-free survival [PFS] of 11.1 months) versus just over six months (PFS of 6.9 months) for those receiving chemotherapy (pemetrexed/cisplatin).

Furthermore, NSCLC patients with tumors harboring the two most common EGFR mutations (del19 and L858R, accounting for 90% of all tumors with EGFR mutations) taking afatinib lived for 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. More of the patients who took afatinib experienced an improvement in shortness of breath, cough, and chest pain, which are typically symptoms in NSCLC patients, and deterioration delay of these symptoms, as well as overall improved quality of life. The safety profile was also encouraging for afatinib, as adverse events were controlable and the discontinuation rate was low.

Based on available clinical trial data in NSCLC patients, it is difficult to accurately compare afatinib with the currently available EGFR inhibitors, as continuous advancement in disease diagnosis and care standards can clarify any differences. Interestingly, Boehringer Ingelheim has already initiated two head-to-head trials (LUX-Lung 7 and 8) comparing afatinib to Iressa (gefitinib) and Tarceva (erlotinib), respectively, to demonstrate any potential efficacy and safety superiority of afatinib.

The trials’ findings will be highly anticipated and give a more exact outlook for the drug’s positioning and success. If afatinib demonstrates superiority in these clinical trials, Boehringer Ingelheim will have a very strong drug candidate for the treatment of NSCLC patients. In case afatinib shows equivalence or inadequacy, there will be more hurdles in gaining market share and Boehringer Ingelheim will have to modify pricing and marketing approaches accordingly. Unquestionably, the approval of afatinib will further increase the competitiveness of this market segment.

GlobalData (London, UK), an international market research company, estimates the global NSCLC therapeutics market is currently worth approximately USD 5 billion and is forecast to reach USD 9.5 billion by 2018. Notably, AstraZeneca’s (London, UK) USD 500 million drug Iressa (gefitinib) and Roche’s (Basil, Switzerland) USD 1 billion drug Tarceva (erlotinib) are major market players. However, sales for Tarceva also include use for pancreatic cancer. Boehringer Ingelheim is also trying to assess the drug’s potential to treat other cancer patient groups. Afatinib has reached phase III clinical development in head and neck cancer and breast cancer, and if the trials findings are optimistic, Boehringer Ingelheim will seek additional approvals.


GlobalData expects Boehringer Ingelheim to receive the EMA’s opinion during the second quarter of 2013, which most likely will be a positive one after taking into consideration the safety and efficacy profile of afatinib. But most significantly, the approval of afatinib will be a key milestone for Boehringer Ingelheim, as it will become the company’s first marketed anticancer agent, and an notable success story for the company’s R&D shift into the oncology therapy area. With two more anticancer drugs being developed, nintedanib for NSCLS and ovarian cancer, and volasertib for acute myeloid leukemia, in later stages of clinical development, Boehringer Ingelheim demonstrates the firm’s go-getting drive to expand in the oncology therapy area and bolster its product range.

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