Ionis Pharmaceuticals, Inc. and partner AstraZeneca Plc announced on July 9, 2026, that the Phase III CARDIO-TTransform trial of Wainua (eplontersen) did not meet its primary efficacy endpoint in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The news triggered a sharp decline in shares, with Ionis falling $20.19, or 23.9%, to close at $64.27, wiping out over $3.3 billion in market capitalization, while AstraZeneca shares dropped more than 8% in premarket trading. Wainua had been positioned as a key value driver toward AstraZeneca's stated "$80 billion 2030 ambition." Following the disclosure, law firms Hagens Berman, Levi & Korsinsky, and Pomerantz LLP launched investigations into potential securities law violations concerning both companies.
Hagens Berman is investigating whether Ionis was sufficiently transparent about the trial’s data and design, specifically focusing on when management knew about problems with the trial or its design. The firm noted that just last month, Ionis touted the study as "the largest study ever conducted by far" in ATTR-CM and assured investors that "everything is going very well." Levi & Korsinsky is examining whether the companies adequately disclosed risks prior to the readout, noting that on AstraZeneca's Q2 2025 earnings call, management described the readout as a highly anticipated catalyst. Pomerantz LLP is investigating claims on behalf of investors concerning whether Ionis and certain of its officers and/or directors have engaged in securities fraud or other unlawful business practices.
Trial Results and Subgroup Analysis
The CARDIO-TTransform study compared the composite outcome of cardiovascular mortality and recurrent cardiovascular clinical events up to Week 140 against a placebo. A prespecified subgroup analysis of patients treated with eplontersen monotherapy compared to placebo showed a nominally significant hazard ratio of 0.71 on the composite outcome. Conversely, no treatment effect was observed in patients who were on stabilizer therapy at baseline. At baseline, 57% of participants in both treatment groups were receiving stabilizer therapy, while another 24% in each arm started a stabilizer during the study. One analyst noted that over 80% of participants were on a stabilizer, driving the failure of the primary endpoint.
| Trial Feature |
Details |
| Participants |
1,432 |
| Study Sites |
130 sites in 20 countries |
| Randomization |
1:1 (Eplontersen 45 mg vs Placebo) |
| Dosing Frequency |
Every four weeks |
| Primary Endpoint |
Composite of CV mortality and recurrent CV clinical events through Week 140 |
Analysts Say Existing Therapies Benefit
William Blair noted the miss was surprising given the combination use benefit reported in the HELIOS-B trial of Amvuttra. The failure of CARDIO-TTransform removes a competitor from the ATTR-CM market and is viewed as positive for existing therapies. These include Alnylam Pharmaceuticals Inc.’s Amvuttra (vutrisiran), BridgeBio Pharma Inc.’s Attruby, and Pfizer Inc.’s tafamidis. Analyst Myles R. Minter indicated physician discussions already suggested second-generation therapies like Attruby and Amvuttra are differentiated from first-generation tafamidis. The results reinforce the view that combining a silencer with a stabilizer does not improve outcomes, supporting monotherapy and benefiting treatments like Intellia Therapeutics Inc.’s nexiguran ziclumeran.
Management Commentary and Future Steps
Brett P. Monia, Ph.D., chief executive officer of Ionis, stated that the findings reflect the rapidly evolving treatment landscape where contemporary ATTR-CM patients are widely treated with stabilizers. Monia emphasized that despite the disappointment regarding the primary endpoint, the results have the potential to guide the treatment landscape. Ionis and AstraZeneca will continue to analyze the full data set, with results to be shared at the European Society of Cardiology (ESC) Congress in August 2026.
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