Boehringer Ingelheim has enrolled its first patient and initiated a phase III study (POLO-AML-2) investigating volasertib, a selective and potent polo-like kinase (Plk) inhibitor, in combination with chemotherapy, in patients with acute myeloid leukaemia (AML) ineligible for intensive therapy.

Acute leukaemias are rare diseases, with AML being the most deadly acute leukaemia in adults. More than 60 countries around the world will join to raise awareness for those affected by rare diseases. In Europe, rare disease is defined as a life-threatening or chronically debilitating disease which affects fewer than five people per 10, 000.

Professor Klaus Dugi, corporate senior vice president Medicine, Boehringer Ingelheim said, "Rare diseases are often incorrectly diagnosed and even once they are correctly diagnosed, there is often a lack of viable treatment options." Professor further added, "The initiation of the POLO-AML-2 trial is a significant milestone as therapeutic options are limited in AML patients ineligible for intensive therapy."

AML is characterised by the rapid proliferation of abnormal blood precursor cells that accumulate in the bone marrow and interfere with the production of normal blood cells. The primary endpoint of POLO-AML-2 is objective response to the combination treatment compared to the chemotherapy alone. The main secondary endpoint of POLO-AML-2 is overall survival.

The study was initiated following positive results from a phase II study which demonstrated higher rates of objective response and an improvement in event free survival in patients receiving volasertib in combination with chemotherapy versus chemotherapy alone.

"Boehringer Ingelheim is committed to developing innovative medications that improve patients’ lives and has put considerable effort into research and development of treatments for orphan† diseases," said Professor Klaus Dugi, corporate senior vice president Medicine, Boehringer Ingelheim.

In addition to AML, Boehringer Ingelheim is investigating therapeutic approaches for other rare diseases including idiopathic pulmonary fibrosis (IPF). IPF is a severely debilitating and fatal respiratory disease. It is characterised by progressive loss of lung function ultimately leading to the death of half of the patient population two to three years after diagnosis.

Nintedanib, a small molecule tyrosine kinase inhibitor (TKI), targets growth factor receptors which have been shown to be potentially involved in the pathomechanism of pulmonary fibrosis. The pivotal INPULSIS-1 and INPULSIS-2 phase III trials have completed recruitment and are ongoing in study centres worldwide to assess the clinical outcomes in IPF patients treated with nintedanib. The phase III INPULSIS trials aim to build upon the promising results of the phase II TOMORROW trial, which demonstrated a positive trend in reducing lung function decline in IPF patients treated with 150 mg of nintedanib twice daily when compared to placebo. Additionally, nintedanib has received orphan-drug designation from the US Food and Drug Administration in June 2011 and by the Ministry of Health, Labour and Welfare of Japan in September 2011.

Volasertib, an inhibitor of Plk, is currently being evaluated in clinical trials for AML and is one of several late-stage compounds that Boehringer Ingelheim is currently evaluating in clinical trials for cancer.

Of the company’s ongoing research in cell cycle inhibition, the volasertib clinical development programme is the furthest advanced. Boehringer Ingelheim is one of the first companies to advance Plk inhibitors into clinical development.

Volasertib is designed to inhibit the activity of Plk. Plk1 – the best characterised of the five known human Plks – is an enzyme that regulates cell division (mitosis). This inhibition results in cell cycle arrest and ultimately cell death (apoptosis).5

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are only limited treatment options available to date. IPF is characterised by progressive scarring of lung tissue and loss of lung function over time. Development of scarred tissue is called fibrosis. Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream, and vital organs do not get enough oxygen. As a result, individuals with IPF experience shortness of breath, cough and often have difficulty participating in everyday physical activities.

Nintedanib is an investigational small molecule tyrosine kinase inhibitor (TKI) in Phase III development by Boehringer Ingelheim for IPF. It targets growth factor receptors, which have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis, most importantly the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR). By blocking these signaling pathways that are involved in fibrotic processes, it is believed that nintedanib* has the potential to reduce disease progression, slowing the decline of lung function. Nintedanib is also in clinical development as a treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.

The current focus of research includes compounds in three areas: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition. Nintedanib is currently in phase III clinical development in non-small cell lung cancer (NSCLC) and ovarian cancer. In the area of signal transduction inhibition, afatinib is currently in phase III clinical development in NSCLC, breast cancer and head and neck cancer.

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

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. The company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.