Cetuximab Biosimilars are on the Horizon

Cetuximab (Erbitux), an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody used to treat metastatic colorectal cancer, metastatic non—small cell lung cancer, and head and neck cancer, was approved by the FDA in 2004, and US patents for the drug expired in 2016 (EU patents expired in 2014). In 2015, Bristol-Myers Squibb transferred North American marketing rights of biosimilar cetuximab to collaborator Eli Lilly. However, despite reported 2016 sales of $1.7 billion, the originator cetuximab has no approved biosimilar challengers in the US or European market.

Multiple drug makers, however, are in the process of developing biosimilar candidates to challenge the brand-name Erbitux’s sales:

• Amgen: the drug maker reported at the 36th Annual J.P. Morgan Healthcare Conference that it is in phase 1 development of a cetuximab biosimilar.
• BioXPress: this Swiss developer reports that cetuximab is a “future program.”
• Celltrion: the Republic-of-Korea-based Celltrion is developing CT-P15 as a cetuximab biosimilar.
• MabTech-Sorrento: in 2016, MabTech-Sorrento announced that it had successfully completed phase 3 clinical trials for STI-001, a “biosimilar-biobetter” cetuximab.

As developers work toward biosimilars of this drug, the reference product sponsor is well on its way to expanding indications for the innovator product; in 2012, the FDA granted approval to cetuximab for use in combination with folinic acid, fluorouracil, and irinotecan (FOLFIRI chemotherapy) for first-line treatment of patients with K-ras mutation-negative (wild-type) EGFR-expressing metastatic colorectal cancer.

Additionally, currently ongoing is a phase 2 trial to investigate the combined usage of afatinib (Gilotrif) in patients with an EGFR-mutated lung cancer. Afatinib is an irreversible EGFR tyrosine kinase Inhibitor (TKI) that binds to its receptor permanently. Unlike other EGFRs, afatinib inhibits the kinase activity of all human epidermal growth factor receptors. The goal of the study is to determine whether the combination of the 2 drugs will either delay or decrease the appearance of treatment resistance.