Phase 3 trial shows Wainua fails to improve outcomes in ATTR-CM, hazard ratio 1.14

AstraZeneca and Ionis Pharmaceuticals presented detailed results from the Phase 3 trial of their antisense oligonucleotide Wainua (eplontersen) in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The data, released at the European Society of Cardiology meeting, confirmed that the drug did not meet its primary endpoint when added to standard of care.

Analysts had previously expected a strong chance of approval after an earlier data drop suggested only modest benefit. The initial release had already caused concern, but the companies did not disclose specific efficacy numbers at that time.

The new analysis showed a hazard ratio of 1.14 for the composite outcome compared with patients receiving only tafamidis (Pfizer’s Vyndamax). This translates to a 14% higher event rate for patients on Wainua, which Stifel described as "clearly worse than expected."

The negative readout represents a significant setback for the TTR silencer program and is likely to weigh on investor sentiment toward both AstraZeneca’s and Ionis’ amyloidosis pipelines.