DREAM Drops Flop

MAY 04, 2016
Ellen Kurek
Regorafenib (Stivarga, Bayer) is an oral anti-angiogenic agent approved by the FDA for the treatment of metastatic colorectal cancer. It is a multi-kinase inhibitor that targets vascular endothelial growth factor (VEGF2/3) receptors, which are known to play a primary role in the progression of wet AMD. It also targets platelet-derived growth factor β (PDGFR-β) receptors.
Because of these effects, a topical form of the drug was evaluated in 51 patients with neovascular (NV) or wet age-related macular degeneration in the DREAM trial, a combined phase 2a/b trial. However, the trial was terminated after phase 2a owing to a lack of efficacy, explained DREAM team member Antonia Joussen, MD, Charité University of Medicine Berlin, at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Seattle, WA, on May 4, 2016. DREAM’s results were also published in an abstract included in the ARVO proceedings.
Joussen asked, “Do we really want to inject eyes over and over again? Isn’t it much easier to have an eye drop? We had this dream. So why did we choose regorafenib?” Joussen explained that the drug was very potent in all preclinical studies. Although not water soluble, it dissolves in liquid paraffin. So studies of topical regorafenib were done in rats and monkeys, as well as by using laser choroidal NV models.
After completing these studies, the team decided to pursue clinical trials. No safety issues in humans emerged in phase 1, so the team began a multicenter, single-arm, open-label phase 2a/b trial to first prove their concept and then determine which dose of regorafenib to use in phase 3.

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