Zaltrap

Drug Overview

Zaltrap is a human recombinant fusion protein comprising segments of the human VEGFRs 1 and 2
and the Fc portion of the human immunoglobulin G1 (Tang et al., 2008). Zaltrap acts as a soluble
decoy receptor that blocks the binding of VEGF to its receptor. This inhibits essential functions
required for tumor cell survival including angiogenesis and metastasis (Rudge et al., 2007). Preclinical
findings following the administration of Zaltrap in mouse and human models were encouraging,
demonstrating effective growth inhibition of tumor cells and angiogenesis suppression (Holash et al.,
2002). Zaltrap is shown to have higher binding affinity to the VEGF-A, VEGF-B, and placental growth
factor than its natural receptors (Fischer et al., 2007). Equilibrium studies have suggested that Zaltrap
binds to VEGF-B with a higher affinity than Avastin (Holash et al., 2002).

Analyst Outlook

Zaltrap (aflibercept; Regeneron/Sanofi) is a vascular endothelial growth factor (VEGF) inhibitor
currently approved for metastatic colorectal cancer (mCRC) patients previously treated with
oxaliplatin. By seeking approval in the second-line setting, Zaltrap was able to minimize direct
competition with Avastin (bevacizumab; Genentech/Roche/Chugai), which targets the same molecular
pathway. However, debates surrounding the high cost of Zaltrap and competition from marketed
VEGF-targeted therapies have severely impacted uptake, with US sales of Zaltrap falling 25% to $29m
between 2013 and 2014. Ongoing clinical trials suggest Sanofi’s effort to increase Zaltrap’s uptake
through label expansions. Nonetheless, concerns regarding Zaltrap’s price, combined with the recent
approval of VEGF receptor (VEGFR) inhibitor Cyramza (ramucirumab; Eli Lilly) for second-line mCRC,
are likely to prevent significant sales growth for the drug.