Dr. Georg Fertig, Roche, Penzberg, Germany
Monoclonal antibodies are meanwhile the most target specific drugs on the market. Due to this, the failure during preclinical and early stage development is low compared to small molecules, which makes them very attractive. Nevertheless, the molecules have to be selected very carefully and small differences in binding behavior could lead to dramatic differences in the mode of action and efficacy. This was for example shown very clearly during preclinical and later clinical phase III studies of Gazyva (Obinutuzumab) conducted in chronic lymphocytic leukemia (CLL).
In this study, Rituxan (the standard of care antibody) was compared to Gazyva, which are both anti-CD20 antibodies binding to an overlapping epitope. The differentiated binding of Gazyva to CD20 finally paid out dramatically. The chlorambucil-Gazyva-combination helped patients live a median of 26.7 months without their cancer progressing, compared to 15.2 months for the Rituxan-plus-chlorambucil combination. This shows how a minimal but diverse binding property could translate into a big difference in efficacy. The presentation will give an overview on the process of antibody discovery with respect to generation of diversity, screening hits and selection of leads within Roche LMR.
