AstraZeneca gambles in amyloidosis

The phase 3 Cares study of AstraZeneca’s AL amyloidosis project anselamimab ended in failure last year, but the company has quietly filed it with regulators anyway. The move was revealed in CHMP documentation showing that Astra had submitted anselamimab for marketing in the EU. Last July Cares failed on its primary endpoint of all-cause mortality and frequency of cardiovascular hospitalisations versus placebo in the overall population, but Astra claimed that it did show an improvement “in a prespecified subgroup of patients”. It’s not clear whether approval is being sought in this subgroup. Anselamimab is a MAb that targets immunoglobulin light chain-related fibrils, and Astra argued that Cares was the first pivotal trial to show that depleting amyloid fibrils can be effective in an amyloid-driven disease. The molecule has a convoluted history, having been originated by academia before being licensed by Fortress Biotech, which then spun it into a subsidiary, Caelum Biosciences. In 2019 Alexion paid $150m for a minority stake in Caelum, before itself being bought by Astra. In 2021 Astra paid $150m for the remainder of Caelum, with a further $350m dependent on regulatory and commercial milestones. Astra hasn’t commented on anselaminab’s approvability in the US.