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  • Print publication year: 2018
  • Online publication date: January 2018

13 - Avastin and Lucentis: Both for Eyesight in Hindsight

Summary

Since its approval in 2004, Avastin (bevacizumab) has achieved a dominant position in the pharmaceutical industry. It is one of the World Health Organization's 100 “essential medicines,” listed under “Ophthalmological Preparations.” In and of itself that's notable, but what makes Avastin unusual is that it was first approved by the FDA for something that most of us would think is completely different: colorectal cancer (CRC). In fact, although it has since been approved for several metastatic cancers, it still has yet to be approved by the FDA for the treatment of eye diseases – the off-label use that makes it so significant in the eyes of the WHO. That privilege belongs to Lucentis (ranibizumab), Avastin's near equivalent, the same drug minus a bit, which was actually approved by the FDA for ophthalmic applications. Our story here concerns how and why this near duplication came about, and what the implications are for drug development and the incentives that drive it and pricing.

STAUNCHING THE FLOW

Avastin is a humanized therapeutic monoclonal antibody (mAb) directed against vascular endothelial growth factor (VEGF), a signal protein required for the initiation and growth of blood vessels (Figure 13.1). It recognizes VEGF-A, a specific version of VEGF, to abolish its activity through the formation of an Avastin-VEGF-A complex. Avastin, by forming a tight association with VEGF-A, blocks its interaction with membrane receptors (VEGFR-1 and VEGFR-2) whose VEGF-mediated activation is necessary for de novo and restorative angiogenesis. Avastin effectively puts a stranglehold on the growth of solid tumors and metastasis by putting a block on vascularization and staunching blood flow. When used to treat cancer, anti-VEGF agents promote regression of existing microvessels and inhibit neovascularization necessary for the provision of adequate oxygen and nutrients for tumor growth and for the entry of tumor cells into the bloodstream for metastasis. Though not equally effective against all solid tumors, Avastin has proven sufficiently effective against several to remain a mainstay for cancer treatment. In addition to metastatic CRC – the cancer against which it has been used most widely – Avastin has been approved for the treatment of lung, brain, cervical, and ovarian cancers.