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Roche and their partner Biogen Idec have just achieved the FDA ‘breakthrough’ designation for their cancer drug GA101, now named Gazyva, a month ahead of the FDA’s stated decision date of December 20th. Gazyva, which was developed by the Roche-owned Genentech, is a successor to Roche’s multi-billion dollar selling drug Rituxan (rituximab) and is designed to treat patients with chronic lymphocytic leukaemia (CLL). Both of these drugs are CD20 monoclonal antibodies but Phase III clinical data shows that, in combination with the chemotherapeutic drug chlorambucil, Gazyva was more effective than Rituxan in extending survival of CLL patients without any worsening of their cancer and Gazyva plus chlorambucil was more than twice as effective as chlorambucil alone in effecting progression-free survival. The news is all the more welcome to Roche as biosimilars from other companies are likely to begin to eat into sales of Rituxan. Industry analysts estimate that Gazyva will be worth $1.5 billion to $2.5 billion a year to Roche at peak sales.

As anti-CD20 antibodies, GA101 and rituximab target cancer cells. However, pre-clinical data already indicated that GA101 was more effective than rituximab in harnessing the immune system in fighting tumour progression in in vitro assays, particularly in terms of antibody-dependent cell-mediated cytotoxicity (ADCC). This enhanced ADCC activity has been linked to the decreased ability of GA101 to fix complement relative to rituximab. In serum, complement blocks rituximab-induced natural killer (NK) cell activation but not GA101-induced ADCC. In SU-DHL4 and RL xenografts in vivo models, GA101 was strongly anti-tumourigenic and effected complete tumour remission in the SU-DHL4 model. Its overall efficacy was superior to both rituximab and ofatumumab, another approved anti-CD20 antibody, and it remained able to control tumour progression in animals that had been pre-treated with rituximab whereas the tumours were resistant to second-line treatment rituximab treatment. Meanwhile, Phase II data on GA101 was positive in terms of both efficacy and safety of the drug.

The Phase III data on cancer-free survival has ensured the drug’s breakthrough designation for CLL, but Roche and Genentech are confident it will have applicability in other blood cancers. Medical chief Hal Barron stated: "We have spent 20 years researching blood cancer medicines, and we will continue to study Gazyva to assess its efficacy in other types of blood cancers."

Sources
HERTER, S. et al., 2013. Preclinical Activity of the Type II CD20 Antibody GA101 (Obinutuzumab) Compared with Rituximab and Ofatumumab In Vitro and in Xenograft Models. Molecular Cancer Therapeutics, 12(10), pp. 2031-2042

KERN, D.J. et al., 2013. GA101 induces NK-cell activation and antibody-dependent cellular cytotoxicity more effectively than rituximab when complement is present. Leukemia & lymphoma, 54(11), pp. 2500-2505

MORSCHHAUSER, F.A. et al., 2013. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. Journal Of Clinical Oncology: Official Journal Of The American Society Of Clinical Oncology, 31(23), pp. 2912-2919

RADFORD, J. et al., 2013. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). Blood, 122(7), pp. 1137-1143

http://www.fiercebiotech.com/story/roche...2013-11-01 [Accessed 3 November 2013].

http://www.fiercebiotech.com/story/roche...2013-07-24 [Accessed 3 November 2013].