AstraZeneca's Wainua Fails Late-Stage Heart Disease Trial, Analysts Flag Study Design Concerns

The setback dims prospects for a drug analysts predicted could have some $2 billion in peak sales, and is another blow for AstraZeneca after a U.S. regulatory panel in May rejected its breast cancer ‌drug camizestrant on trial ⁠design grounds.

AstraZeneca, ⁠which is counting on up to 20 new drug launches to help generate $80 billion in annual revenue by 2030, said Wainua did not meet the main goal of reducing cardiovascular deaths and recurring heart problems in a late-stage trial for patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).

"Data comes as a surprise given we and investors hadn't even debated likelihood of a primary endpoint miss, ​given positive precedent data and successful launch for competitor Amvuttra," BofA analyst Sachin Jain said, referring to rival Alnylam Pharmaceuticals' drug.

AstraZeneca shares fell nearly 10% to the lowest level since November last year. At 1448 GMT the drugmaker was down 7.7%, still the biggest loser on the FTSE 100 index on Thursday. The stock is ​on course for its biggest one-day percentage drop since November 2024 having lost £23.3 billion ($31.21 billion) in market ⁠value at ‌the day's low.

"While the news is relatively small to AstraZeneca's valuation, the effect is much greater on the company's own gold standard ​of design trials success," ​said Lucy Coutts, Investment Director at JM Finn, an AstraZeneca shareholder. "In simple terms, investors expect AstraZeneca to succeed, and this ⁠is why the share price has taken such a hit and future expectations may be tempered."

Shares of ​U.S.-listed partner Ionis fell nearly 21% while U.S. competitors Alnylam and BridgeBio, which have approved drugs for ATTR-CM, ​climbed between 6% and 16%.

FLAWED TRIAL DESIGN MASKS BENEFITS

Wainua was being tested in 1,432 patients for the condition that involves protein build-up in the heart that disrupts blood pumping and can cause heart and organ failure, affecting 300,000 to 500,000 people globally, AstraZeneca said.

The trial showed that adding the drug to standard care did not provide a statistically significant benefit. Taking it as a standalone therapy without stabilizers showed "nominally significant" benefit, it said.

Current treatments for the condition, including Pfizer's Vyndaqel, work by stabilizing the faulty proteins that accumulate in the heart. Wainua and Amvuttra work by reducing production of the proteins.

Analysts criticised the 140-week trial's design where 57% ‌of patients were already taking a stabilizer, and a further 24% added a stabilizer during the study, which made it difficult to assess any benefit from the drug.

Jefferies analysts said the design flaw could dent management credibility after executives expressed strong confidence in the ​trial's prospects.

"(AstraZeneca) is meant ​to be able to have exceptionally good trial ⁠design ability," Jefferies said, adding that the trial miss should not derail the company's long-term revenue target.

ANALYSTS DO NOT EXPECT A NEW MONOTHERAPY TRIAL

The trial was keenly followed by analysts and investors as a key step in AstraZeneca accessing an underpenetrated ATTR market and building on growth through its existing strong pipeline.

"Although ​the trial did not meet its primary objective, we believe the results support greater scientific understanding of treatment approaches," said Sharon Barr, executive vice president of AstraZeneca's biopharmaceuticals R&D.

Barclays analysts said they do not expect AstraZeneca to fund a new monotherapy trial for Wainua, as that would be unlikely to get an approval this decade and would be too far behind the well-established rival drug from Alnylam.

Wainua, which generated $212 million in product revenue for AstraZeneca in 2025, is already approved in more than 20 countries to treat patients with polyneuropathy, a life-shortening rare disease that causes nerve damage.