Both AstraZeneca and Ionis’ stocks took a hit at market open on 9 July after the companies announced that a Phase III trial of Wainua (eplontersen) in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not meet its primary efficacy endpoint.
The CARDIO-TTRansform study (NCT04136171) failed to meet the composite outcome of cardiovascular (CV) mortality and recurrent CV clinical events up to 140 weeks in patients treated with Wainua compared to those who received placebo.
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The results deal a blow to a potential indication expansion for Wainua, which is already approved in more than 20 countries to treat patients with polyneuropathy, a rare disease that affects nerve tissue.
Wainua was generally well tolerated in CARDIO-TTRansform, with a safety profile consistent with previous results.
Patients were treated with standard of care (SoC), including a majority on a stabiliser; however, the addition of Wainua did not provide a statistically significant benefit on the composite outcome.
In a prespecified subgroup analysis of patients treated with Wainua monotherapy as compared to placebo, fewer primary composite events (CV mortality and recurrent CV events) were observed, and this result was nominally significant. In patients who were on stabiliser therapy at baseline, no treatment effect was observed.
Sharon Barr, executive vice president, BioPharmaceuticals R&D at AstraZeneca, said: “The CARDIO-TTRansform trial was designed to examine the role of Wainua, a gene silencer treatment, on top of today’s standard of care in reducing recurring cardiovascular events and mortality. Although the trial did not meet its primary objective, we believe the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients worldwide suffering from this progressive and often fatal condition.”
AstraZeneca and Ionis will analyse the full data set to further understand the results, which will be shared with the scientific community at the European Society of Cardiology (ESC) Congress in August 2026.
AstraZeneca’s stock took a significant hit at market open on the London Stock Exchange on 9 July, from an 8 July close of £142.40 ($190.76) to an open of £123.88 – a 13% decrease. There has been some recovery during the day, with the stock price sitting at £130.70, correct at 2.17pm BST.
Ionis has seen an even more significant drop in its stock value. The company, listed on the Nasdaq exchange, opened 19% down on 9 July at $68.38, compared to an $84.46 close on 8 July.
Wainua first gained approval in December 2023 for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN or ATTRv-PN) in adults. It is an antisense oligonucleotide (ASO) designed to silence the production of transthyretin (TTR) protein.
While this is a significant blow to AstraZeneca and Ionis, the news will likely be uplifting for Alnylam’s Amvuttra (vutrisiran), as it became the first gene-silencing RNA interference (RNAi) therapeutic to gain a label expansion for use in ATTR-CM. The drug was first approved in 2022 for the treatment of polyneuropathy in adults with hereditary transthyretin-mediated amyloidosis, but the label was expanded in March 2025 to include ATTR-CM.
Other competitors in the ATTR-CM space include Pfizer’s Vyndamax (tafamidis), a once daily oral protein stabiliser, and BridgeBio’s Attruby (acoramidis), a small-molecule TTR stabiliser.
Jefferies analysts suspect that AstraZeneca’s failure was likely impacted by the high proportion of patients in the control group who received Vyndamax during the study, with 24% being prescribed the drug during the trial, taking the 57% of patients on the drug at baseline closer to 80% by the end of the study. They noted this to be significantly higher than the 53% of control patients who had been on Vyndamax in Alynlam’s study.
ATTR is a protein conformational disorder caused by the build-up of transthyretin, the protein carrying thyroxine and retinol in the bloodstream. While cardiomyopathy is a characteristic of patients with wild-type ATTR (ATTR-wt), some patients with hereditary ATTR (ATTR-h) also experience cardiomyopathy symptoms along with their polyneuropathy.
