AstraZeneca Shares Sink After Heart Drug Trial Miss. Rare Clinical Setback Tests Investor Confidence

AstraZeneca shares fell sharply Thursday after the pharmaceutical giant reported that its experimental use of Wainua failed to achieve the primary endpoint in a late-stage clinical trial for a rare heart disease, marking an unusual setback for one of the industry’s most consistent drug developers during a period when healthcare companies continue to navigate investor caution amid geopolitical uncertainty, persistent inflation and ongoing pressure on global healthcare spending.

The British drugmaker said Wainua did not significantly reduce cardiovascular deaths or recurrent heart-related events compared with placebo in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a progressive disease caused by abnormal transthyretin protein deposits in the heart muscle. The findings came from the Phase III CARDIO-TTRansform trial, AstraZeneca said in a company announcement Thursday.

London-listed AstraZeneca shares dropped as much as 9% during trading before trimming some losses, putting the stock on track for its worst trading session since the early stages of the COVID-19 pandemic. U.S.-listed shares also declined sharply, while partner Ionis Pharmaceuticals recorded steeper losses after the trial results were announced, according to CNBC.

The study evaluated whether adding Wainua to existing treatment could improve outcomes for patients with ATTR-CM over 140 weeks. The trial failed to meet its primary objective despite AstraZeneca previously expressing confidence in the study’s design and potential benefit, Reuters reported.

Jefferies analysts said the failed study was unlikely to derail AstraZeneca’s target of reaching $80 billion in annual revenue by 2030. However, the analysts said management’s confidence before the data release could raise questions among investors after the primary endpoint was missed.

Wainua, marketed as Wainzua in Europe, is already approved in multiple countries for treating hereditary transthyretin-mediated polyneuropathy (ATTRv-PN), a different form of transthyretin amyloidosis in which abnormal protein deposits primarily damage peripheral nerves rather than the heart. AstraZeneca said the existing approval remains unchanged following the latest trial outcome. The company also said complete results from the study will be presented at the European Society of Cardiology Congress in August, AstraZeneca stated this in its announcement.

ATTR cardiomyopathy has increasingly become a focus for major pharmaceutical companies as improved diagnosis has revealed the disease to be more common than previously believed. The condition causes abnormal transthyretin protein deposits to stiffen the heart muscle, eventually leading to heart failure. Industry estimates suggest roughly half a million people worldwide may be living with the disease, according to Financial Times.

The trial results also reshaped the competitive landscape for ATTR-CM therapies. Existing treatments include Pfizer’s Vyndamax, BridgeBio’s protein stabilizer, and Alnylam Pharmaceuticals’ gene-silencing therapy Amvuttra. Following AstraZeneca’s announcement, shares of Alnylam and BridgeBio rose while Ionis shares fell sharply.

AstraZeneca said 57% of patients enrolled in the study were already receiving a transthyretin stabilizer at the start of the trial, while another 24% began stabilizer therapy during the study. Among patients who were not taking a stabilizer at baseline, Wainua demonstrated what the company described as a “nominally significant” reduction in deaths and cardiovascular events compared with placebo. However, those findings were not enough for the overall study to achieve its primary endpoint, AstraZeneca said.

Analysts also pointed to the trial design as an important factor in the outcome. The high proportion of patients already receiving background stabilizer therapy made it more difficult to demonstrate additional clinical benefit from Wainua, Reuters reported.

In a statement released with the trial results, Sharon Barr, executive vice president of BioPharmaceuticals R&D at AstraZeneca, said that although the study did not meet its primary objective, the findings contribute to scientific understanding of treatment strategies for patients living with the progressive disease.