Boehringer Ingelheim has long been associated with treatments for stroke prevention, COPD and HIV/AIDS, but not cancer. That’s about to change, if a cornucopia of 13 abstracts presented at the European Society for Medical Oncology (ESMO) is any evidence.

Closest to market is afatinib, an oral tyrosine kinase receptor inhibitor, which is currently in Phase III clinical development in advanced non-small cell lung cancer (NSCLC), head and neck cancer, and breast cancer. Next is likely to be nintedanib, an oral triple angiokinase inhibitor that is also in Phase III clinical development in NSCLC and ovarian cancers. A third candidate for which early stage trial data were presented is volasertib, an inhibitor of polo-like kinase.

Kevin Lokay, who heads BI’s oncology franchise (and whom MM&M interviewed last month) had this to say about the company’s preparation to build its oncology footprint:

“Our commitment to enter the oncology space over 20 years ago has resulted in a robust oncology pipeline with investigational agents in all stages of clinical and pre-clinical development, including several in Phase III trials, that address a variety of targets across a range of tumor types. These are targeted therapies that can lead to a more personalized approach to lung cancer treatment, with the goal of improved patient outcomes. The rigor and breadth of the data we presented at the ESMO 2012 Congress, which include patient-reported health-related outcomes from the pivotal Phase III trial, LUX-Lung 3, demonstrate our commitment to oncology patients and their families.”

“Commitment is crucial when developing personalized cancer therapies,” Lokay continued. “Boehringer Ingelheim is focused on bringing a broad range of potential therapies to patients through its diverse pipeline.”

The financial community also is starting to take note of BI’s moves. Dr. Marc Engelsgjerd, senior analyst, inThought Research sees the data as an encouraging milestone in BI’s gear-up to participate in this market: “Boehringer has a very extensive lung cancer program for Afatnib which is great to see because they are asking a lot of different questions, looking at different combinations and patient subsets. That’s really the right way to develop a drug; you have to make sure you don’t leave any stone unturned.”

Among the multiple abstracts presented during ESMO, the one the company spotlighted is the afatinib LUX-Lung 3 results, a pivotal Phase III trial that demonstrated a significant progression-free survival (PFS) advantage vs. standard chemo and impressive quality of life improvement among first-line treatment of advanced NSCLC patients with an EGFR mutation.

According to a company representative, “Results of the LUX-Lung 3 trial — the largest trial of patients with EGFR mutation-positive advanced NSCLC — showed a median improvement in PFS of 11.1 months (the primary endpoint) with afatinib within the general study population, versus 6.9 months for those patients treated with pemetrexed/cisplatin, which is considered a standard chemotherapy in advanced and metastatic lung cancer.”

Dr. Engelsgjerd points out that the LUX-Long 3 trial has resuscitated hopes for the development of this candidate: “In lung cancer, Afatnib had a failed trial a couple of years ago, but the most recent positive study — the LUX long 3 study — has really renewed interest and made people focus again on the potential of this compound.”

Based upon these datasets, BI is working on marketing applications for afatinib in a number of countries in the US and EU. The company was unable to comment on whether it would seek accelerated approval for the product.

Dr. Engelsgjerd added: “The LUX Lung-3 data was impressive in terms of the PFS benefits. We’ll have to wait until next year to see if there is an overall survival benefit. Part of me is wondering if regulatory bodies will want to hold out for an overall survival benefit. I assume Boehringer will want to push ahead for approval and there is precedent for that.”

Lokay is keen to point out that the strategy behind the compound is a personalized one. “The strategy behind afatinib is to focus on developing a personalized therapy for patients who can benefit from the treatment.”

In keeping with this approach, the LUX Lung 3 trial incorporated a diagnostic test to confirm an EGFR mutation status and mutation. BI has partnered with Qiagen to develop a real-time polymerase chain reaction assay (real-time PCR) companion diagnostic. Of note, between 10-15% of Caucasians and approximately 40 percent of Asians with NSCLC have EGFR mutations – 90 percent of which are the result of two mutations (Del19 or L858R). In Lokay’s words, “We’ve taken the personalized medicine approach further … to develop a companion diagnostic to determine a patient’s biomarker status to better matching their unique genetic profile with an appropriate targeted therapy, like afatinib.”

The question now is how these assets will fare in comparison to existing treatments for NSCLC, which include Avastin (bevacizumab), marketed by industry heavyweight Genentech, Tarceva (erlotinib), which is co-marketed by Genentech and Astellas Oncology, and AstraZeneca’s Iressa (gefitinib).

“There are other lung cancer studies with Afatnib where they are pitting it against Tarceva and Iressa. Those are gutsier trials but those are the exact kind of trials we need to see more of because it’s one thing to show that your drug works against placebo but the relevant question is, is it better that what is currently being used,” asks Dr. Engelsgjerd. “Many companies shy away from those types of studies but lung cancer is a crowded space and Boehringer really has to swing for the fences.”

From a promotional standpoint, the company already has launched an unbranded disease awareness program called Let’s Test, which is designed to educate HCPs and the oncology community about the important role of biomarker testing.

Lokay notes, “Five or six years ago, there were a relatively low number of patients who were tested for biomarkers in cancer. With advances in personalized medicine and the discovery of unique biomarkers — like EGFR, ALK and HER2 — this number has increased, but not all lung cancer patients are tested. It is our hope that biomarker testing will become an immediate first step that a doctor takes when diagnosing a patient with lung cancer. We want it to be automatic, or reflexive, which means that the oncologist will be able to get the right treatment to the right patient at the right time. In fact, the aim of our ‘Let’s Test’ program is to encourage the adoption of biomarker testing as standard practice and thereby increase the frequency of testing. We’re encouraging a multidisciplinary approach by working with physicians involved in the diagnosis process, such as pulmonologists, pathologists and oncologists, to demonstrate the importance of biomarker testing with the goal of improving patient outcomes.”

Another effort the company has made to carve a footprint out in the category is in building an online community called My Cancer Circle — a free, private, customizable tool for caregivers of people facing cancer. Company market research found that while the information needs of patients themselves was largely satisfied, there was an unmet need for information among caregivers. The company collaborated with CancerCare, a patient advocacy organization, to build the tool, which helps caregivers organize and coordinate support from their circle of family and friends. According to Lokay, “We are excited that to date, over 100 private communities, or ‘circles,’ have been created.”

At the end of the day, the company recognizes that the health care system is no longer simply rewarding innovation, but is looking for value. In response to how BI plans to position its franchise for optimal success in light of the Affordable Care Act, Lokay points out, “Boehringer Ingelheim is committed to providing patients who currently have limited treatment options with therapies that have a demonstrated value. As a company committed to the health of patients and their families, we are not aiming to develop treatments that work 10% of the time, in 90% of the population – but rather products that work 90% of the time, in 10% of the population.”

See on www.mmm-online.com