Shares of AstraZeneca AZN fell nearly 8% in pre-market trading today after the company announced the failure of a phase III study evaluating Wainua (eplontersen) in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The company is co-developing this drug with Ionis Pharmaceuticals IONS, whose stock also slumped 19% following the announcement.
The late-stage study, called CARDIO-TTRansform, failed to meet its primary endpoint of the composite outcome of cardiovascular (CV) mortality and recurrent CV clinical events. Although the drug was well tolerated in study participants over a 140-week treatment period, adding Wainua to the standard of care did not demonstrate a statistically significant benefit compared to placebo.
The CARDIO-TTRansform study outcome comes as a surprise, as investors were expecting positive results. Wainua is already approved for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN), a condition in which misfolded transthyretin (TTR) protein deposits damage peripheral nerves.
ATTR-CM is caused by the same misfolded TTR protein but primarily affects the heart, where amyloid deposits accumulate in the heart muscle, leading to progressive CV disease. Success in ATTR-CM was expected to significantly expand Wainua’s commercial opportunity, as the ATTR-CM market is considerably larger than the ATTRv-PN market.
Both companies plan to analyze the full data set to better understand the results and intend to present the findings at the European Society of Cardiology (ESC) Congress next month.
AZN Stock Performance
Shares of AstraZeneca have underperformed the industry so far this year, as seen in the chart below.
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Rivals Rally on AZN’s Setback
Following AstraZeneca/Ionis’ update, shares of Alnylam Pharmaceuticals ALNY and BridgeBio Pharma BBIO rose about 18% and 11%, respectively, in pre-market trading on Thursday. With Wainua failing to meet the primary endpoint in the CARDIO-TTRansform study, AstraZeneca’s entry into the ATTR-CM market now faces uncertainty. Investors appear to view the setback as strengthening the near-term competitive position of ALNY and BBIO.
BridgeBio’s Attruby was approved by the FDA for ATTR-CM in 2024, while Alnylam’s Amvuttra received a label expansion for the indication last year. Both companies are well positioned in the rapidly growing ATTR-CM market, where effective disease-modifying therapies remain in high demand.
While Amvuttra was initially approved for the treatment of ATTRv-PN, its label expansion into ATTR-CM significantly broadened the drug’s commercial opportunity. The expanded approval helped Amvuttra achieve blockbuster status, with sales surging 138% year over year to $2.31 billion in 2025, underscoring the sizable commercial potential of the ATTR-CM market. Meanwhile, BridgeBio generated $362.4 million in Attruby sales during the drug’s first full year on the market, reflecting the strong demand for therapies targeting the disease.