Apellis fails to complement severe Covid-19

Hitting complement activation looks to follow inhibition of Jak and GM-CSF in being crossed off the list of mechanistic approaches to treat severe Covid-19. Yesterday Apellis said it was canning its complement C3 inhibitor APL-9 in severe Covid-19 after a phase I/II study found no meaningful reduction in mortality. This came on the heels of similar failures from Alexion’s anti-C5 MAb Ultomiris and Inflarx’s C5a-targeting IFX-1. Complement forms part of the innate immune response to viruses and triggers inflammation, so the idea was that inhibiting it could reduce cytokine activation and prevent lung damage, along the lines that have seen anti-IL-6 antibodies tested in Covid-19. This was backed by mouse studies showing that activation of complement C3 exacerbated disease in Sars, and as early as February 2020 Alexion was proposing to use Soliris to manage severe pneumonia associated with Covid-19. Given the successes of antibodies, not to mention vaccine roll-outs, the failure of the complement mechanism probably matters little at this stage, but it does leave up in the air the fate of ongoing complement inhibitor trials being run by UCB, Innate Pharma and Pharming.