AstraZeneca (AZN) Stock Falls 9% After Wainua Heart Drug Trial Fails

TLDR

• AstraZeneca stock dropped as much as 9% after its heart drug Wainua failed a late-stage clinical trial
• Wainua did not meet its goal of reducing deaths and heart events in ATTR-CM patients over 140 weeks
• 57% of trial patients were already on stabilizer therapy, masking any additional benefit from the drug
• Analysts flagged a trial design flaw rather than a fundamental drug failure, but raised credibility concerns
• Ionis Pharmaceuticals fell 13.8% in premarket; rival Alnylam surged 17%

---

AstraZeneca stock fell as much as 9.1% in London trading on Thursday, its worst single-day drop since March 2020, after its heart disease drug Wainua failed to hit its primary goal in a late-stage clinical trial.

AstraZeneca PLC, AZN

NYSE-listed AZN shares were down 8.4% in premarket trading, wiping roughly £23.3 billion ($31.21 billion) off the company’s market value at the day’s low.

The drug was being tested in 1,432 patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a rare condition where misfolded proteins build up in the heart, making it harder to pump blood. An estimated 300,000 to 500,000 people live with the condition globally.

Wainua failed to show a statistically significant reduction in cardiovascular deaths and recurring heart problems over 140 weeks compared to a placebo, AstraZeneca said in a press release Thursday morning.

Trial Design Comes Under Fire

The result caught analysts off guard. Most had not expected a primary endpoint miss, given positive data from rival drug Amvuttra, made by Alnylam Pharmaceuticals.

The problem appears to be how the trial was set up. A total of 57% of patients were already taking a stabilizer drug at the start of the study, and another 24% started one during the trial. Since stabilizers work differently to Wainua — a so-called gene silencer — stacking the two treatments made it hard to measure any additional benefit.

For patients not on a stabilizer at baseline, Wainua did show a “nominally significant” benefit. But that subgroup result was not enough to meet the trial’s main goal.

Jefferies analysts said AstraZeneca “is meant to be able to have exceptionally good trial design ability,” and that the failure on design grounds would hit management credibility. The bank now models for $2.5 billion less in risk-adjusted sales for the drug.

BofA analyst Sachin Jain called the result “a surprise,” noting that investors had not even considered a miss scenario given the competitor data already on the market.

What Comes Next for Wainua

Barclays said they do not expect AstraZeneca to fund a new monotherapy trial for Wainua, as that path would be unlikely to reach approval this decade and would lag too far behind Alnylam’s already well-established drug.

Citi analysts added that filing for additional approvals for Wainua in ATTR-CM now looks unlikely, with Alnylam’s Amvuttra already holding a treatment for the condition.

Wainua’s existing license remains unaffected. The drug is already approved in more than 20 countries for polyneuropathy — a nerve-damaging condition — and generated $212 million in product revenue for AstraZeneca in 2025.

Jefferies maintained that the miss does not threaten AstraZeneca’s $80 billion annual revenue target by 2030, which depends on up to 20 new drug launches. The analysts noted the stock may not recover until results from the AVANZAR cancer trial are published.

U.S.-listed partner Ionis Pharmaceuticals fell 13.8% in premarket trading. Alnylam climbed 17% and BridgeBio rose between 11% and 16%.

AstraZeneca said the results “support greater scientific understanding of treatment approaches” for ATTR-CM patients.