Eplontersen hits – but how hard?

Astrazeneca and Ionis are to file eplontersen for hereditary transthyretin-mediated amyloid polyneuropathy after a planned interim analysis in the phase 3 Neuro-TTRansform trial came out positive. The antisense oligonucleotide achieved a statistically significant and clinically meaningful change from baseline in serum transthyretin concentration versus what Astra called “an external placebo group” – historical control. It also hit the trial’s other co-primary endpoint, change from baseline on mNIS+7 score, a measure of neuropathic disease progression, versus external placebo. The partners have not disclosed the extent of eplontersen’s success, but a look at the three approved therapies for this subtype of transthyretin amyloidosis shows the sort of thing doctors will be looking for. It should be noted that unlike Neuro-TTRansform, the pivotal trials of these drugs did contain placebo arms. The control in Neuro-TTRansform was in fact Ionis’s own approved Tegsedi; so far no data on this arm have been released. Stifel analysts write that the extent of the improvement on mNIS+7 is crucial, and safety, described by Astra as “favourable”, with no specific concerns, will also be important given that Tegsedi’s label has a black box warning for thrombocytopenia and glomerulonephritis.