AbbVie Presents Results from Phase 2 Study of Investigational Compound Venetoclax (ABT-199/GDC-0199) in Acute Myelogenous Leukemia at the 56th American Society of Hematology Annual Meeting

- AbbVie Presents for the First Time Results from the Venetoclax Phase 2 Program in Acute Myelogenous Leukemia

- Study Evaluated Preliminary Efficacy of Venetoclax in 32 Patients with Relapsed/Refractory Acute Myelogenous Leukemia and as Frontline Therapy in Patients Unfit for Intensive Treatment

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AbbVie

Dec 07, 2014, 08:15 ET

NORTH CHICAGO, Ill., Dec. 7, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) presented during an oral presentation at the American Society of Hematology's 56^th Annual Meeting new results from a Phase 2 study of investigational compound venetoclax (ABT-199/GDC-0199) in patients with acute myelogenous leukemia (AML). AML is an aggressive and deadly type of blood cancer, in which the body produces too many of a specific type of white blood cell (myeloblast), which can crowd out healthy blood cells.¹ In the study, the venetoclax group showed an overall response rate (ORR) of 15.5 percent, with one patient achieving a complete response and four patients achieving a complete response with incomplete blood count recovery.

A complete response (CR) is sometimes called complete remission, and refers to the disappearance of all signs of cancer in response to cancer treatment.² A complete response with incomplete blood count recovery (CRi) is when a patient fulfills most – but not all – criteria to be classified as a complete response. CRi indicates activity but is not the same as a complete response.³

"Acute myelogenous leukemia is an aggressive cancer with low survival rates, and there is a high need among patients and healthcare providers for new, effective treatment options," said Marina Konopleva, M.D., Ph.D., associate professor of the Department of Leukemia, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center. "The results of this trial of venetoclax are encouraging and warrant additional study in patients with AML."

"This is the first time we have reported results from the venetoclax Phase 2 clinical trial in AML. We believe venetoclax's potential in this indication warrants further investigation," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie. "The results from this study and AbbVie's other abstracts presented during ASH represent the continued progress of our strong blood cancer development program and demonstrate our commitment to discovering innovative treatment options."

About the Study
The Phase 2, open-label, multicenter clinical trial was designed to evaluate the preliminary efficacy of venetoclax in 32 patients with relapsed/refractory AML or as frontline therapy for patients who are unfit for intensive therapy. Secondary objectives included safety and pharmacodynamics assessments.

Isocitrate dehydrogenase (IDH) mutations are genetic mutations found in a small number of patients with AML and may influence outcomes.⁴ IDH mutations were found in three patients who achieved CR/CRi. Two of these patients also achieved minimal residual disease (MRD) negativity, which represents a response to a given therapy and describes the detection of zero leukemic cells during treatment or after a patient is in remission.⁵

Additionally, researchers assessed patients' bone marrow myeloblast (blast, or immature white blood cells) counts. A bone marrow blast count of greater than 20 percent is generally required for a diagnosis of AML and reduction of blasts indicate a diminished presence of leukemia.⁶ The median bone marrow blast count in evaluable patients treated with venetoclax decreased 36 percent. Of note, six patients (19%) had at least a 50 percent bone marrow blast reduction.

Common adverse events (≥25% of patients) included nausea, diarrhea, fatigue, neutropenia and vomiting. Grade 3 and 4 adverse events (in ≥3 patients) included febrile neutropenia, anemia and pneumonia.

These data indicate that further study of venetoclax in AML patients is warranted. Venetoclax will be studied in combination with other medicines sometimes used in treating patients with AML. Development and evaluation of the compound in several blood cancers is ongoing.

About Venetoclax (ABT-199/GDC-0199)
Venetoclax is an investigational inhibitor of the B-cell lymphoma-2 (BCL-2) protein being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be highly expressed in cancers in the lymph nodes, spleen and other organs of the immune system. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein, leading to restoration of the communication system that tells cancer cells to self-destruct. Venetoclax is being developed in collaboration with Genentech in the United States and Roche outside the United States. Together, the companies are pioneering BCL-2 research with venetoclax, which is currently being evaluated in a Phase 3 clinical trial for the treatment of CLL and several other cancers. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.

About Acute Myelogenous Leukemia (AML)
Acute myelogenous leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow and is one of the most common types of leukemia among adults. In AML, the body produces too many of a specific type of white blood cell (myeloblast), which can crowd out healthy blood cells.1 Approximately 19,000 new cases of AML were diagnosed in 2014 in the U.S. and more than 10,000 deaths were attributed to the disease in 2014.⁷

About AbbVie Oncology
AbbVie's oncology research is focused on the discovery and development of targeted therapies that work against the processes cancers need to survive. By investing in new technologies and approaches, we are breaking ground in some of the most widespread and difficult-to-treat cancers, including multiple myeloma and chronic lymphocytic leukemia. Our oncology pipeline includes multiple new molecules in clinical trials being studied in more than 15 different cancers and tumor types. For more information on AbbVie Oncology and our oncology portfolio, please visit http://oncology.abbvie.com.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

¹"Acute Myeloid Leukemia" The U.S. National Library of Medicine. http://www.nlm.nih.gov/medlineplus/acutemyeloidleukemia.html Accessed October 14, 2014.
² National Cancer Institute website. "NCI Dictionary of Cancer Terms." http://www.cancer.gov/dictionary?CdrID=45652. Accessed October 30, 2014.
³ Cheson, B. D. et al. (2003) "Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia." J Clin Oncol. 21:4642-4649.
⁴ Rakheja D, Konoplev S, Medeiros LJ, et al. (2012) "IDH mutations in acute myeloid leukemia." Journal of Human Pathology. Retrieved October 14, 2014.
⁵ Buccisano, F. et al. (2012) "Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia." Blood. 119:332-341.
⁶ "How is acute myeloid leukemia diagnosed?" American Cancer Society. http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia-acute-myeloid-myelogenous-diagnosed. Accessed October 16, 2014
⁷ "What are the key statistics about acute myeloid leukemia" American Cancer Society. http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia-acute-myeloid-myelogenous-key-statistics. Accessed October 14, 2014.