Value through Innovation16 April 2014
10 December 2012

Boehringer Ingelheim to initiate Phase III study in leukaemia with its compound volasertib* based on positive Phase II results

• Phase II study demonstrated higher rates of objective response and an improvement in event free survival (EFS) in patients with acute myeloid leukaemia (AML) receiving volasertib* in combination with low-dose cytarabine (LDAC) versus LDAC alone
• Phase III study of volasertib* in AML is planned to be initiated in early 2013

Ingelheim, Germany, 10 December, 2012 – New positive Phase II results from an interim analysis of the randomised Phase I/II study involving the company’s investigational haematology/oncology compound volasertib* in newly diagnosed patients with acute myeloid leukemia (AML) considered ineligible for intensive remission induction therapy were presented at the 54th American Society of Hematology (ASH) annual meeting in Atlanta, USA. In this study, higher rates of objective response (primary endpoint) and an improvement in event free survival (secondary endpoint) were observed in patients treated with volasertib*, a selective and potent polo-like kinase (Plk) inhibitor, in combination with low-dose cytarabine (LDAC) compared to patients treated with LDAC alone.1 Based on these positive results Boehringer Ingelheim announced the initiation of a Phase III study of volasertib* in combination with LDAC (POLO-AML-2 (1230.14)), which is expected to start in early 2013.

The open-label study enrolled 87 adult patients randomly assigned to receive either volasertib* in combination with LDAC (n=42) or LDAC alone (n=45). The primary endpoint was objective response (complete remission [CR] or CR with incomplete blood count recovery [CRi]). Objective responses were observed in 31 percent of patients (13 of 42 patients) treated with the combination of volasertib* plus LDAC compared with 13.3 percent of the patients (6 of 45 patients) treated with LDAC alone (odds ratio: 2.91; p = 0.0523). The median (range) time to remission was 71 (29–158) days and 64 (30–125) days, respectively.1

Secondary endpoints included event-free survival (EFS), overall survival (OS) and safety. EFS was measured from the date of randomisation to the date of disease progression (treatment failure), relapse or death from any cause, whichever occurred first. In patients treated with the combination of volasertib* plus LDAC, the median EFS was 5.6 months compared with 2.3 months in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, .93; p=0.0237).1

Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

"The results from this trial provide insight into the potential of volasertib* combined with LDAC in patients with AML not eligible for intensive induction chemotherapy," said Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "Based on the results observed in this difficult-to-treat patient population, we are expanding our volasertib* haematology clinical programme to further explore this investigational compound."

An increased frequency of higher grade adverse events (AEs) (CTCAE grade 3-5) was observed in patients treated with volasertib* plus LDAC compared to LDAC alone (95.2 vs. 68.9%). Focusing on the AEs of higher severity, the difference was most prominent for blood and lymphatic system disorders (81% vs. 44.4 %), gastrointestinal disorders (21.4% vs. 6.7%), and infections (47.6% vs. 22.2%). This was expected given the mechanism of action of volasertib*.1

Acute leukaemias are rare diseases, with AML being the most common type of leukemia in adults.2 There is currently a high unmet medical need in AML, which has the lowest survival rate of all leukaemias.2 The goal of treatment for patients with AML is to reduce the number of blast cells in the bone marrow and return to normal blood counts. The most common treatment approach is intensive remission induction therapy; however, many patients over 65 years of age are ineligible for this approach which involves large doses of chemotherapy over a period of five to seven days.3

Boehringer Ingelheim intends to begin recruitment of a Phase III study (NCT01721876) to assess the efficacy and safety of volasertib* in combination with LDAC compared with LDAC alone in early 2013. The planned Phase III trial, POLO-AML-2, will enroll eligible patients aged 65 or older with previously untreated AML who are ineligible for intensive remission induction therapy. For additional information on the trial, please visit ClinicalTrials.gov.

Notes to Editors

About Volasertib*
Volasertib*, an investigational inhibitor of polo-like kinase (Plk), is one of several late-stage compounds that Boehringer Ingelheim is currently evaluating in clinical trials for various solid tumors and haematological cancers.

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 Plk1, an enzyme that regulates cell division (mitosis). This inhibition is intended to result in prolonged cell cycle arrest and ultimately cell death (apoptosis).4

About Acute Myeloid Leukemia (AML)
While AML is one of the most common types of leukaemia in adults, accounting for 25 percent of all adult leukaemias in the Western world, it is a rare cancer of the bone marrow and the blood.2,5 AML has one of the lowest survival rates of all leukemias.2

AML is primarily a disease of later adulthood; the average age of newly diagnosed patients is 65 years.2 In AML patients over the age of 65 the prognosis is poor, with a median survival of 6 months or less following diagnosis.6

About Boehringer Ingelheim in Oncology
Building on scientific expertise and research 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 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. 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 soon to move in to 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.

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.

In 2011, Boehringer Ingelheim achieved net sales of about 13.2 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

For more information please visit:
www.thewhiteroom.info and www.newshome.com

*Volasertib, afatinib and nintedanib are investigational compounds. Their safety and efficacy have not yet been fully established.

References

1 H. Döhner, Phase I/II study of volasertib (BI 6727), an intravenous Polo-like kinase (Plk) inhibitor, in patients with acute myeloid leukemia (AML): results from the randomized phase II part for volasertib in combination with low-dose cytarabine (LDAC) versus LDAC monotherapy in patients with previously untreated AML ineligible for intensive treatment. Oral Presentation at ASH Annual Meeting and Exposition 2012.
2 Deschler B et al. Acute Myeloid Leukemia: Epidemiology and Etiology. Cancer. 2006. 2009-2107.
3 Texas Oncology. Acute Myeloid Leukemia Induction, Overview. Available at: http://www.texasoncology.com/types-of-cancer/leukemia/acute-myeloid-leukemia/acute-myeloid-leukemia-induction/ [Last Accessed: November 2012]
4 Schöffski P. Polo-Like Kinase (PLK) Inhibitors in Preclinical and Early Clinical Development in Oncology. Oncologist. 2009;14(6):559-570.
5 Macmillan, What is acute myeloid leukaemia? Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Leukaemiaacutemyeloid/AboutAML/WhatisAML.aspx [Last Accessed: November 2012]
6 Juliusson G et al, Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood April 30, 2009 vol. 113 no. 18 4179-4187

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