Perjeta

Drug Overview

Perjeta is a humanized MAb that binds to subdomain II of the extracellular part of the HER2 protein.
Binding blocks ligand-dependent heterodimerization of HER2 with other HER family members,
including epidermal growth factor receptor, HER3, and HER4 (Perjeta prescribing information, 2015).
Perjeta inhibits ligand-initiated intracellular signaling through the mitogen-activated protein kinase
pathway and the phosphoinositide 3-kinase pathway. Preclinical tumor mouse xenograft models with
HER2-positive cells have demonstrated Perjeta’s antitumor activity in gastric cancer. In particular, the
combination of Perjeta plus Herceptin was shown to have enhanced antitumor efficacy compared
with single-agent therapy with either drug (Jorgenson, 2014).

Analyst Outlook

Perjeta (pertuzumab; Roche/Chugai) is a humanized monoclonal antibody (MAb) under development
for the treatment of metastatic gastric cancer expressing human epidermal growth factor receptor 2
(HER2). Perjeta has a distinct but complementary mechanism of action to Herceptin (trastuzumab;
Roche/Chugai). Preclinical models and early-phase clinical trials have demonstrated a potential
synergistic antitumor effect. Perjeta represents an important opportunity for Roche and Chugai to
maintain their dominance of the HER2-positive gastric cancer market, as looming patent expiries
threaten to erode branded sales of Herceptin and new HER2-targeted therapies attempt to penetrate
the market. However, the cost of treatment with Perjeta plus Herceptin and chemotherapy is expected
to be high. Phase III trials of Perjeta will have to demonstrate especially significant improvements in
patient outcomes in order to win favor in cost-conservative markets.