Boehringer Ingelheim Presents New Phase II Data for Volasertib in Adult Patients with AML

RIDGEFIELD, Conn., Dec. 10, 2012 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today reported preliminary results from the randomized Phase II part of a Phase I/II study involving the company's investigational compound volasertib in newly diagnosed patients with acute myeloid leukemia (AML) considered ineligible for intensive remission induction therapy.  In this study, higher rates of objective response (primary endpoint) and a trend for longer median event free survival (EFS) (a secondary endpoint) were observed in patients treated with volasertib in combination with low-dose cytarabine (LDAC) compared to patients treated with LDAC alone.¹  Presented at the 54^th American Society of Hematology (ASH) annual meeting in Atlanta, Ga., these results support the initiation of a Phase III study of volasertib in combination with LDAC expected to start in early 2013. 

AML is one of the most common types of leukemia in adults.²  A common treatment approach is intensive chemotherapy to induce disease remission, followed by consolidation/maintenance chemotherapy.^3,4  However, many patients over 65 years of age – whose prognosis is typically poor⁵ – are ineligible for this approach, which involves large doses of chemotherapy over short periods of time.^3,4 

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 randomization 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 approximately 5.6 months (170 days) compared with approximately 2.3 months (69 days) in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, 0.93; p=0.0237).  Follow-up for overall survival was ongoing at the time of this analysis.¹   

"The preliminary 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 Berthold Greifenberg, M.D., vice president, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc.  "Based on the results observed in this difficult-to-treat patient population, we are expanding our volasertib hematology clinical program to further explore this investigational compound." 

In the volasertib plus LDAC treatment arm (n=42), grade 5 non-hematologic adverse events (AEs) were infections (5%), febrile neutropenia (5%) and respiratory/thoracic/mediastinal events (7%).  Grade 3/4 non-hematologic AEs were gastrointestinal events (19/2%), general events (14/2%), infections (38/5%), febrile neutropenia (38/7%), metabolism/nutrition events (10/5%) and respiratory/thoracic/mediastinal events (14/2%).  In the LDAC monotherapy arm (n=45), grade 5 non-hematologic AEs were infections (9%), and grade 3/4 non-hematologic AEs were gastrointestinal events (7/0%), general events (16/2%), infections (7/7%), febrile neutropenia (4/9%), metabolism/nutrition events (7/0%) and respiratory/thoracic/mediastinal events (11/2%).¹ 

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.⁶  For additional information on the trial, please visit ClinicalTrials.gov.

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 hematological cancers.

Of the company's ongoing research in cell cycle inhibition, the volasertib clinical development program 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).⁷

Volasertib is not approved by the FDA; its safety and efficacy have not been established.

About Acute Myeloid Leukemia (AML)
AML is a cancer of the bone marrow and the blood.⁸  It is one of the most common types of leukemia in adults, accounting for 25 percent of all adult leukemias in the Western world,⁹ and has one of the lowest survival rates of all leukemias.²

AML is primarily a disease of later adulthood; the average age of an AML patient is 65 years.¹⁰  In patients diagnosed with AML at age 65 or older, the prognosis is poor.⁵

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 program to develop innovative cancer treatments. Working in close collaboration with the international scientific community and a number of the world's leading cancer centers, Boehringer Ingelheim's commitment to oncology is underpinned by using advances in science to develop a range of targeted therapies for various solid tumors and hematological cancers.

The current focus of late-stage research includes compounds in three areas: signal transduction inhibition, angiogenesis inhibition and cell-cycle kinase inhibition.

For information about participating in a Boehringer Ingelheim clinical trial, please visit www.bicancertrials.com or call 1.866.725.7110. Healthcare providers interested in learning more about Boehringer Ingelheim clinical trials in oncology can visit www.inoncologyus.com for additional information.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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 has a demonstrated commitment to corporate social responsibility. 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 endeavors.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

References
¹ Dohner H. 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 The Leukemia and Lymphoma Society. Facts 2012. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/generalcancer/pdf/facts.pdf [Last Accessed: November 21, 2012]

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 21, 2012]

⁴ Texas Oncology. Acute Myeloid Leukemia Consolidation, Overview. Available at: http://www.texasoncology.com/types-of-cancer/leukemia/acute-myeloid-leukemia/acute-myeloid-leukemia-consolidation/ [Last Accessed: December 4, 2012]

⁵ The Leukemia and Lymphoma Society. Acute Myeloid Leukemia: Treatment Outcomes. Available at: http://www.lls.org/#/diseaseinformation/leukemia/acutemyeloidleukemia/treatment/outcomes/. [Last Accessed: November 1, 2012]

⁶ ClinicalTrials.gov.  Volasertib in Combination With Low-dose Cytarabine in Patients Aged 65 Years and Above With Previously Untreated Acute Myeloid Leukaemia, Who Are Ineligible for Intensive Remission Induction Therapy.  ClinicalTrials.gov Identifier: NCT01721876. Accessible here: http://clinicaltrials.gov/ct2/show/NCT01721876?term=1230.14&rank=1 [Last Accessed: November 13, 2012].

⁷ Schoffski P.  Polo-Like Kinase (PLK) Inhibitors in Preclinical and Early Clinical Development in Oncology.  Oncologist. 2009;14(6):559-570.

⁸ Cleveland Clinic. Adult Acute Myeloid Leukemia. Available at: http://my.clevelandclinic.org/disorders/acute_myeloid_leukemia/hic_adult_acute_myeloid_leukemia.aspx. [Last Accessed: November 1, 2012]

⁹ Deschler B et al. Acute Myeloid Leukemia: Epidemiology and Etiology. Cancer. 2006. 2009-2107.

¹⁰ National Marrow Donor Program. Acute Myelogenous Leukemia (AML). Available at: http://marrow.org/Patient/Disease_and_Treatment/About_Your_Disease/AML/Acu te_Myelogenous_Leukemia_(AML).aspx#MakingTreatmentDecisions. [Last Accessed: November 1, 2012]

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.