Boehringer Ingelheim’s volasertib showed in a Phase II study an improvement in overall survival in older AML patients

Summary:
Acute Myeloid Leukaemia (AML) is an aggressive and devastatingblood cancer.^1,2 It predominantly affects people over 60 and is one of the most common adult leukaemias in the Western World.¹ The current standard of care is intensive chemotherapy, but many older patients cannot tolerate this therapeutic approach; their options are limited and their prognosis is poor. For older AML patients not suitable for intensive chemotherapy, low dose cytarabine (LDAC) is a well-established form of chemotherapy. Volasertib*, currently being developed by Boehringer Ingelheim, showed in recent studies to be a potentially promising alternative treatment for these patients. In this Phase II clinical trial volasertib*, combined with LDAC, led to prolonged survival times and more than doubled the percentage of patients achieving remission compared to LDAC alone. Volasertib* is currently being investigated in combination with LDAC in a Phase III clinical trial.

Ingelheim, Germany, July 8 2014 – Results from a Phase II study, published (today) in the American Society of Hematology journal Blood,³ showed patients with previously untreated acute myeloid leukemia (AML) aged 65 or older and ineligible for intensive remission induction therapy, lived longer when treated with volasertib* combined with low dose cytarabine (LDAC), a form of chemotherapy, compared to LDAC alone. The overall survival data showed that volasertib*, when used in combination with LDAC, increased the percentage of older AML patients who achieved remission.

“Despite being a rare disease, AML is one of the most common leukaemias in adults and predominantly affects older people. The established approach to treat younger AML patients is an intensive chemotherapy regimen, called intensive induction therapy. However, older patients often cannot tolerate these chemotherapy doses, and have very limited treatment options,” commented Prof. Döhner from the Department of Internal Medicine III of the University Hospital Ulm and principal investigator of the Phase II trial. “These clinical trial results that evaluated volasertib in combination with a lower intensity chemotherapy are important and have informed future research for this rare disease, where new treatment options are greatly needed.”

The Phase II clinical trial showed patients treated with volasertib* combined with LDAC had a median overall survival of 8 months versus 5.2 months in patients treated with LDAC alone. The response rate (complete remission or complete remission with incomplete blood count recovery) was more than doubled for patients receiving volasertib* and LDAC versus LDAC alone (31% versus 13.3%).

Volasertib* is an investigational compound that inhibits enzymes called Polo-like kinases (Plks). Plk1 is the best characterized kinase of the Plk family. Inhibition of Plk1 by volasertib* ultimately results in cell death (apoptosis).⁴ By inhibiting Plk1 activity, the extremely high cell division that is characteristic of AML should be blocked, which may result in cancer regression.

The most common non-haematological adverse events for patients receiving the combination treatment were decreased white blood cells with fever and infections and gastrointestinal side effects. These side effects were clinically manageable and were expected given the mechanism of action of volasertib*.^3,5

“As with other rare and life threatening diseases, the need for new treatment options in AML is very high. Boehringer Ingelheim is committed to research in areas of unmet medical need, including those in rare diseases.” commented Prof. Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim. “We are pleased to see that volasertib* has shown promising overall survival results in this clinical trial and we are optimistic that the drug will further demonstrate its potential benefit in this rare disease in the ongoing Phase III study.”

Volasertib* was awarded Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) in 2013 and Orphan Drug Designation by the FDA and the European Commission in 2014. It is currently being investigated in combination with LDAC in a randomised, double-blind, multi-centre, controlled Phase III clinical trial for AML called POLO-AML-2.

Indication
Acute Myeloid Leukaemia (AML)

Product
Volasertib*

Notes to editors:

About the volasertib* Phase II results

The results of the Phase II clinical trial published in Blood³ included the following endpoints:
•Response rate (complete remission or complete remission with incomplete blood count recovery) was more than doubled for patients receiving volasertib* and LDAC vs LDAC alone (31% vs 13.3%, 13 of 42 patients vs 6 of 45 patients; odds ratio, 2.91; P=0.052).
•Median event-free survival was prolonged in patients receiving volasertib* and LDAC vs LDAC alone (5.6 months vs. 2.3 months; hazard ratio [HR] 0.57, 95% confidence interval [CI], 0.35–0.92; P=0.021)
•Remissions achieved by the combination appeared to be more durable (the relapse free survival for volasertib* and LDAC vs LDAC alone was 18.5 vs. 10.0 months, 13 vs 6 patients)
•Median overall survival was 8.0 months vs 5.2 months, respectively (HR 0.63, 95% CI, 0.40-1.00; P=0.047).
•Responses in patients receiving volasertib* and LDAC were observed across all genetic groups, including 5 of 14 AML patients with adverse genetics.
•Patients receiving volasertib* and LDAC showed a higher rate of adverse effects (AE), in particular febrile neutropenia grade 3 (38% vs. 7%), infections grade 3 (38% vs. 7%) and gastrointestinal AEs grade 3 (21% vs. 7%).

About volasertib*
Volasertib* is an investigational, selective and potent inhibitor of enzymes called Polo-like kinases (Plks). Plk1, the best understood of the five known Plks, has an important role in cell division.  Inhibition of Plk1 by volasertib* results in cell cycle arrest with subsequent induction of apoptosis (programmed cell death).⁴ Volasertib is currently being evaluated in clinical trials for acute myeloid leukaemia and is one of several late-stage compounds that Boehringer Ingelheim is currently evaluating in clinical trials for the treatment of cancer.

About the POLO-AML-2 Study
POLO-AML-2 (NCT01721876) is a randomised, double-blind, multi-centre, controlled Phase III clinical trial of volasertib* in combination with LDAC in patients aged 65 years and older with newly diagnosed AML, not suitable for intensive induction therapy.

For additional information on the trial, please visit http://clinicaltrials.gov./ct2/show/NCT01721876?term=Volasertib&rank=4

About Acute Myeloid Leukaemia (AML)
Acute myeloid leukaemia is an aggressive and devastating blood cancer mainly affecting people over age 60.2 It is one of the most common types of acute leukaemia in adults, accounting for approximately one third of all adult leukaemias in the Western world1 and with one of the lowest survival rates of all leukaemias.²

In AML patients the prognosis worsens with increasing age, with a median survival of less than a year⁷ following diagnosis. The current standard of care for younger AML patients is intensive chemotherapy. However, 40% of AML patients cannot tolerate this treatment due to their age and comorbidities and the debilitating side effects.⁸ Especially for those older patients there is an unmet medical need for new and effective treatment options.

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: angiogenesis inhibition, signal transduction inhibition and cell-cycle kinase inhibition.Volasertib* is the most advanced pipeline compound for haematological cancers. The pipeline for haematological cancers also includes two new biological entities (NBEs) using an immunotherapeutic approach: BI 836858 is an anti-CD33 antibody targeting AML and BI 836826 is an anti-CD37 antibody targeting chronic lymphocytic leukaemia (CLL) and B-cell non-Hodgkin's lymphoma (B-NHL).

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, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

For more information please visit www.boehringer-ingelheim.com

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