AstraZeneca and Ionis's Wainua misses goal in ATTR-CM outcomes trial

AstraZeneca and Ionis said in July that their silencer eplontersen, sold as Wainua, did not meet the primary endpoint of the Phase 3 CARDIO-TTRansform trial in ATTR-CM.

The study enrolled 1,432 patients at 130 sites in 20 countries. The primary endpoint was a composite of cardiovascular death and recurrent cardiovascular events through week 140. Adding eplontersen to standard care did not produce a statistically significant benefit over placebo, the companies said.

Background stabilizer use was high. Some 57% of patients in each arm were taking a stabilizer at baseline, and another 24% started one during the trial. Patients already on a stabilizer at baseline showed no treatment effect, while a prespecified analysis of eplontersen alone versus placebo showed a nominally significant benefit.

The result has also raised questions about Alnylam's rival silencer, Amvuttra. In Alnylam's own HELIOS-B trial, Amvuttra's benefit in patients already on tafamidis was 21% and not statistically significant. A later JAMA meta-analysis of both silencer trials found no significant benefit in patients on a stabilizer, and Jefferies analysts said the value of silencers had been diminished. In April the FDA also objected to mortality claims on the Amvuttra website.