AstraZeneca PLC (LSE:AZN, NASDAQ:AZN) shares tumbled 9.55% in early trading on Thursday, sending the stock to the top of the FTSE 100 losers’ list.
The sharp decline wiped approximately £19 billion from the pharmaceutical giant’s market valuation in a matter of hours.
The selloff followed news that Wainua, developed with US partner Ionis, had failed the closely watched CARDIO-TTRansform Phase III trial.
The study tested the drug in patients with transthyretin-mediated amyloid cardiomyopathy, known as ATTR-CM, a progressive and often fatal condition in which misfolded protein accumulates in the heart.
The trial did not meet its primary endpoint of reducing cardiovascular deaths and recurrent cardiovascular events over 140 weeks compared with a placebo.
AstraZeneca said adding Wainua to current standard of care, which included a stabiliser treatment for most patients, provided no statistically significant benefit.
In a prespecified subgroup of patients receiving Wainua alone, fewer events were observed and the result was nominally significant, though no treatment effect was seen in patients already receiving stabiliser therapy.
The CARDIO-TTRansform trial was the largest ever conducted in ATTR-CM, enrolling 1,432 patients across 130 sites in 20 countries.
Sharon Barr, head of biopharmaceuticals research and development at AstraZeneca, said that although the trial missed its primary objective, the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients living with the disease worldwide.
Full data from the trial will be presented at the European Society of Cardiology Congress in August, giving analysts and clinicians a more detailed picture of the results.
The Wainua readout was one of three major Phase III catalysts hanging over the stock in the second half, alongside the SERENA-4 trial of breast cancer drug camizestrant and the AVANZAR lung cancer study of Datroway.
Citi, which holds a buy rating on the shares, had modelled peak Wainua sales in ATTR-CM of around $6.2 billion, assigning a 59% probability of success and making it the highest-conviction of the three readouts.
The bank had estimated in May that a failure of CARDIO-TTRansform would knock around 2.8% off its discounted cash flow valuation, equivalent to roughly £5.20 off its £181 fair value estimate.
Citi had also argued that the roughly 10% fall in AstraZeneca shares from their pre-results highs already exceeded the combined 7% downside it attributed to the failure of all three trials.
Even in a scenario where all three readouts disappointed, the bank calculated a bear-case valuation of £168, still 23% above where the shares were then trading.
The broker’s bull case, assuming success across all three trials, pointed to a valuation of around £204 per share.
Today’s sell-off suggests the market is pricing in a harsher read-across, with investors likely reassessing the risk attached to the remaining SERENA-4 and AVANZAR readouts later this year.
Citi has consistently described AstraZeneca as having the best growth and best pipeline in European pharma, citing $46 billion of risk-adjusted peak pipeline sales and ten Phase III readouts due in 2026.
Wainua is already approved in more than 20 countries for the polyneuropathy of hereditary transthyretin-mediated amyloidosis, a separate nerve-damage indication that remains unaffected by today’s trial result.