Roche gets EU ok for Perjeta
06.03.2013 - Swiss Roche has gotten EU approval for Perjeta (pertuzumab). The antibody boosts efficacy of Herceptin by blocking HER dimerisation.
The European Commission gave the green light for a combination therapy of pertuzumab, Herceptin (trastuzumab) and docetaxel in previously untreated adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer. The recommendation for market approval is based on Roche’s Phase III CLEOPATRA study in which the combination therapy prolonged median progression-free survival for 6.1 months compared to Herceptin and chemotherapy alone. Furthermore, the treatment triggered a 34% reduction in the risk of death.
The improvement of Herceptin efficacy by Perjeta is due to a synergistic mode of action of the two antibody drugs. Herceptin blocks homodimerisation of HER2 when HER2 is overexpressed. The antibody prevents activation of HER2-dependent pathways by binding to the extracellular domain IV of the protein and thus blocks MAPK-dependent cell proliferation and PI3K-dependent inhibition of apoptosis. In contrast, Perjeta binds HER2 from the opposite side and prevents heterodimerisation with HER1 and HER3 proteins. Especially, inhibition of HER2/HER3 dimerisation seems important as HER3 supports PI3K-mediated cell proliferation following dimerisation with HER2.
“The EU approval of Perjeta is the result of years of research into the HER2 pathway and we are excited to offer a new treatment option for people with this aggressive disease,” said Roche’s CMO Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. The combination therapy provides a clever strategy for extension of Herceptin’s life cycle. However, Roche is already evaluating a combination therapy of its antibody-toxin warhead T-DM1 with Perjeta.