ABT-199: Novel Bcl-2 Specific Inhibitor Updated Results Confirm Substantial Activity and Durable Responses in High-Risk CLL

MILAN, June 13, 2014 /PRNewswire/ --

Promising results from phase-I study for CLL patients will be presented by Dr John Seymour. 

Chronic Lymphocytic Leukaemia (CLL) is the most common leukemia in adults in the Western world and is diagnosed in approximately 5 persons per 100,000 population per year. Whereas many cancers are associated with rapid proliferation of tumor cells, in contrast CLL is largely a disease of gradual "accumulation", where the leukemic cells have a profoundly prolonged life-span. The mechanism underlying this is an escape from the normal process of physiologic programmed cell death, or apoptosis. The B-cell lymphoma-2 (BCL-2) gene and the derived protein, and related members of the larger family of BCL-2 proteins which share the common "BH3"-binding element in their structure are the regulators of this process of apoptosis and it has long been known that CLL cells overexpress this pro-survival BCL-2 protein.

An oral drug, ABT-199/GDC-0199 was designed to exclusively mimic the binding of this "BH3" structural element exclusively to the BCL-2 protein, hence the drug class designation of "BH3-mimetic". This action restores the regulatory process that tells cancer cells to self-destruct.  The drug is jointly developed by AbbVie and Genentech and is being investigated in a repertoire of studies from phase-I single agent, combination with anti-CD20 monoclonal antibodies and standard chemotherapy, and is in phase-II and -III studies in CLL.

The current presentation updates the results of the CLL arm of the ongoing phase-I single-agent study and establishes;

• The safety of the agent when delivered using a carefully monitored step-wise dose escalation schedule which has largely obviated the earlier risk of rapid tumor destruction with associated chemical imbalances (tumor lysis syndrome; TLS)
• An excellent long-term safety profile with few patients stopping drug due to toxicities beyond the first few weeks of dosing,
• The dose of 400 mg is currently selected for safety expansion, although no formal maximum tolerated dose (MTD) had been defined
• Remarkable efficacy in a patient population with multiply relapsed or refractory disease (overall response rate 77%), with high overall response rates (75 - 79%) and impressive complete remission rates (22 - 29%) and clearance of "minimal residual disease" (MRD) even in the high-risk subsets of patients with the adverse risk del(17p) chromosomal abnormality associated with p53 mutation / dysfunction, an un-mutated immunoglobulin heavy chain gene (IGHV) and those with disease refractory to fludarabine.
• Durable disease control with an actuarial progression free survival of 59% at 24 months for those patients treated at doses of ≥400 mg

Details of these issues are outline in the attached slides summarising the presentation of this data to be presented by Professor John Seymour in the "CLL and related Disorders - Clinical 1" Session 16:15 Sat 14 June in Room Silver (NW Level 2).

Declaration: Prof Seymour has acted as a consultant and member of Advisory Boards to AbbVie, Genentech & Roche.

Presenter: Dr John Seymour

Affiliation: Peter MacCallum Cancer Centre, Australia

Topic: ABT-199: Novel Bcl-2 specific inhibitor updated results confirm substantial activity and durable responses in high-risk CLL.

Abstract S702 will be presented by Dr John Seymour on Saturday, June 14, 2014, 16:15 - 17:30 in Room Silver (NW-Level 2).

About the EHA Annual Congress 

Hematology is a specialty that covers everything to do with blood: its origin in the bone marrow, diseases of blood and their treatments. The latest data on research and developments will be presented. The topics range from stem cell physiology and development, to leukemia, lymphoma, myeloma - diagnosis and treatment; red blood cells -, white blood cells- and platelet disorders; thrombosis and bleeding disorders.