Roche and Ionis bring tominersen back from the dead

Roche is not the first company to persevere with a neuroscience project that previously looked dead and buried, but at least it is going about resurrecting the Huntington’s antisense asset tominersen in the right way. The project, licensed from Ionis, flunked the pivotal Generation HD1 study last year, but Roche now says it has seen a signal in a post-hoc analysis in young adults with a low disease burden. Instead of running another phase 3, or indeed seeking approval, Roche is now going back to phase 2, although details are scant. If the asset is to progress further Roche will need to provide reassurance about worrying findings in Generation HD1: tominersen-treated patients did numerically worse than the placebo group on several clinical measures, with the highest dose performing the worst. And tominersen’s phase 1/2 trial found increases in neurofilament light chain, a marker of neuronal injury; together, these results raise the possibility of toxicity. There is also the theoretical risk that knocking down healthy as well as mutant huntingtin protein might be harmful. Still, with no approved therapies for Huntington’s, and a couple of more recent disappointments, Roche looks justified in trying again.