Abbott Laboratories / Genentech Inc. (Roche Group)

Chronic Lymphocytic Leukemia / B-cell malignancies

Disease Overview

Chronic lymphocytic leukemia (CLL) is a clonal proliferation of mature CD5+ B-lymphocytes driven in large part by overexpression of the antiapoptotic protein BCL-2, which prevents malignant cells from undergoing programmed cell death. It is the most common adult leukemia in Western countries and historically depended on chemoimmunotherapy backbones (FCR, BR) until the arrival of targeted oral agents.

Competitive Landscape

In June 2007 the CLL standard of care was the FCR regimen (fludarabine + cyclophosphamide + Roche/Genentech's Rituxan) along with bendamustine (Treanda) and chlorambucil; for solid tumors the first-line antiangiogenic was Genentech's Avastin (bevacizumab). Abbott's ABT-263 (navitoclax) was a first-in-class oral BH3-mimetic Bcl-2/Bcl-xL/Bcl-w inhibitor with strong preclinical apoptosis induction in CLL, while ABT-869 (linifanib) was a multi-targeted VEGFR/PDGFR tyrosine kinase inhibitor framed as a potential complement to Avastin. The deal granted US co-promotion to both companies with Abbott retaining ex-US, and Phase 1 navitoclax data showed 35% ORR with 25-month median PFS but dose-limiting thrombocytopenia from on-target Bcl-xL inhibition. That toxicity catalyzed Abbott/AbbVie and Genentech's reengineering into the selective Bcl-2 inhibitor ABT-199 (venetoclax/Venclexta), FDA-approved April 2016 for del(17p) CLL — by 2024 venetoclax generated $1.22 billion in sales, validating the 2007 Bcl-2 thesis even though navitoclax itself never reached market for an oncology indication.