The Crowded Field of VEGF and VEGF-R Targeting Drugs
The Business Intelligence firm La Merie S.L. reported that the versatility of the validated VEGF and VEGF-R target and its tractability for all kinds of drug classes has filled the pipeline of VEGF agonists, VEGF/VEGF-R antagonists and VEGF-R tyrosine kinase (tk) inhibitors. Apart from antibody-based constructs and novel binding proteins, other technologies such as small molecules, vaccines, proteins,peptides, gene therapy and RNAi make use of the validated target in markets with growing attractivity. Competitor projects are in all stages of development. These results and more were found in a competitor analysis conducted by La Merie Business Intelligence.
At least seven gene therapy approaches for expression of VEGF are in clinical development to induce neovascularization in cardiovascular and neurological indications. The most advanced projects are in mid-stage development and preclinical followers are about to enter the clinic. Protein approaches to deliver VEGF are preferred for wound healing and erectile dysfunction.
Pegaptanib sodium has been the first approved anti-VEGF drug for treatment of wet age-related macular degeneration (AMD), closely followed by the antibody fragment ranibizumab. Although sales of pegaptanib suffer from off-label use of the anti-VEGF antibody Avastin, at least four clinical stage and six preclinical stage VEGF- and VEGF-R antagonist projects are in the pipeline. The competitor projects are small interfering RNA molecules, DNA, fusion proteins and small molecules and include improved delivery formats such us sub-tenon injections or application as eye drops. Apart from wet AMD other ophthalmologic diseases are in development for VEGF-antagonists to expand the clinical label.
Avastin sales by Genentech and Roche in the first half-year of 2006 were US$ 1.13 bln, 119 % higher than in the corresponding period of 2005, thus representing a rapidly growing blockbuster market. Clinical stage competitors include antibodies and binding proteins targeting the VEGF receptors, and fusion proteins, soluble receptor proteins and RNA targeting VEGF as well as small molecules suppressing VEGF synthesis. Further at least 14 projects consist of products originating from technologies such as vaccines, peptides, proteins, siRNA, DNA and antibody-based constructs. However, the vast majority of competitors for Avastin in oncology are VEGF-receptor tyrosine kinase (tk) inhibitors. More than 30 small molecule VEGF-R-inhibitors including selective, dual- and multi-tk inhibitors are in development, 27 of them in clinical stages.
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