AZ, Ionis Shares Tumble on ATTR‑CM Trial Flop, But Analyst Flags Over‑Reaction Explained

AstraZeneca and Ionis Pharmaceuticals' shares fell sharply after their heart disease drug Wainua (eplontersen) failed to meet the primary endpoint in a late-stage trial for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The trial, called CARDIO-TTRansform, showed the drug did not significantly reduce cardiovascular deaths and heart events when added to standard care over a 140-week period. AstraZeneca's stock fell about 9–10% in London and around 8% in the U.S., while Ionis shares dropped by roughly 12–20% in premarket trading, wiping out billions in market value. The failure clouds prospects for what analysts had estimated as up to ~$2 billion in peak sales for Wainua in ATTR-CM, a competitive market dominated by Alnylam and Pfizer's tafamidis. However, the drug still showed a nominally significant benefit in a subgroup of patients not already on stabilizer therapies, giving some scientific rationale for further study. Analysts from firms like Citi question the prospects for regulatory approval in ATTR-CM, though one noted that the market reaction may be an over-reaction given the drug's earlier success in ATTR polyneuropathy and remaining pipeline value.