Boehringer Ingelheim's investigational volasertib receives FDA Breakthrough Therapy designation

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Sep 17, 2013, 06:00 ET

RIDGEFIELD, Conn., Sept. 17, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced the FDA has granted Breakthrough Therapy designation to volasertib*, an investigational inhibitor of polo-like kinase (Plk), being evaluated for the treatment of patients aged 65 or older with previously untreated acute myeloid leukemia (AML), ineligible for intensive remission induction therapy.

"This FDA Breakthrough Therapy designation provides Boehringer Ingelheim the opportunity to engage in an ongoing dialogue with the FDA to help expedite the development of volasertib as a potential treatment option for these patients with AML," said Sabine Luik, M.D., senior vice president, Medicine & Regulatory Affairs, U.S. Regional Medical Director, Boehringer Ingelheim Pharmaceuticals, Inc. "Volasertib is one of many investigational compounds in Boehringer Ingelheim's growing oncology pipeline and is an example of our commitment to exploring treatment approaches with the goal of improving patient outcomes."

The Breakthrough Therapy designation process was established by the FDA in July 2012 and is intended to facilitate and expedite the development and review of drugs for serious or life-threatening conditions if preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.¹

AML is an aggressive cancer of the bone marrow and blood.² It accounts for 25 percent of all adult leukemias in the Western world³ and has one of the lowest survival rates of all leukemias.³ In 2013, it is estimated there will be 14,590 new cases of AML diagnosed in the U.S. and 10,370 deaths from the disease.⁴

AML is primarily a disease of later adulthood; the average age of an AML patient is 65 years.⁵ A common treatment approach for AML is intensive chemotherapy to induce disease remission, followed by consolidation/maintenance chemotherapy.⁶ However, many patients over 65 years of age – whose prognosis is typically poor⁷ – are ineligible for this approach, which involves large doses of chemotherapy over short periods of time,⁶ and therefore have even fewer treatment options. Volasertib* is currently being investigated in this specific patient population.⁸

Results from a Phase II study, in newly diagnosed patients with AML considered ineligible for intensive remission induction therapy, demonstrated higher rates of objective response and an improvement in event-free survival in patients receiving volasertib in combination with low-dose cytarabine (LDAC) compared to patients receiving LDAC alone.⁹ The results were presented at the 54th American Society of Hematology (ASH) annual in December 2012.⁹

These results led to the initiation in January 2013 of a Phase III trial, POLO-AML-2 (Clinical Trial Identifier: NCT01721876).⁸ This trial is designed to assess the efficacy and safety of volasertib in combination with LDAC, compared to placebo in combination with LDAC, in patients aged 65 or older with previously untreated AML, ineligible for intensive remission induction therapy.⁸The trial is currently enrolling eligible patients.⁸ For more information please visit ClinicalTrials.gov.⁸

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. 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 in the Plk family that regulates cell division (mitosis). This inhibition is intended to result in prolonged cell cycle arrest, ultimately leading to cell death (apoptosis).¹⁰

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

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 discover and 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. The company is also evaluating a robust and growing pipeline of early-stage oncology compounds in areas including growth/survival signaling, immunotherapy and epigenetics.

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 140 affiliates and more than 46,000 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.

Social responsibility is a central element of Boehringer Ingelheim's culture. 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.

In 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

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

*Volasertib is an investigational compound.
Its safety and efficacy have not been established.

References

¹ U.S. Food and Drug Administration. Frequently Asked Questions: Breakthrough Therapies. Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Last Accessed: June 24, 2013.
²Cleveland 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]
³ Deschler B et al. Acute Myeloid Leukemia: Epidemiology and Etiology. Cancer. 2006. 2009-2107.
⁴ The Leukemia and Lymphoma Society. Facts. Spring 2013. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/generalcancer/pdf/facts.pdf. Last Accessed: June 25, 2013
⁵National 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]
⁶ 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]
⁷ 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
⁸ 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 (POLO-AML-2). Available at: http://clinicaltrials.gov/ct2/show/NCT01721876?term=polo-aml-2&rank=1. Last Accessed: June 24, 2013.
⁹ H. Dohner, 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.
¹⁰ Schoffski P. Polo-Like Kinase (PLK) Inhibitors in Preclinical and Early Clinical Development in Oncology. Oncologist. 2009;14(6):559-570.