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# AstraZeneca, Ionis' Wainua Misses Phase 3 Study Endpoint
- URL: https://www.fdaweb.com/astrazeneca-ionis-wainua-misses-phase-3-study-endpoint/
- Published: 2026-07-09T12:00:00.000Z
- Updated: 2026-09-14T13:42:36.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5161432

AstraZeneca and Ionis Pharmaceuticals are reporting that their Phase 3 CARDIO-TTRansform trial evaluating Wainua (eplontersen) in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) failed to meet its primary efficacy endpoint, marking a setback for the companies' effort to expand the drug's use beyond hereditary ATTR polyneuropathy.

The global study found that Wainua did not significantly reduce the composite endpoint of cardiovascular mortality and recurrent cardiovascular clinical events through 140 weeks compared with placebo in patients receiving contemporary standard of care.

According to the companies, the trial enrolled patients who were broadly treated with existing therapies for ATTR-CM, with 57% receiving a transthyretin stabilizer at baseline and another 24% initiating stabilizer therapy during the study. In that setting, adding Wainua did not provide a statistically significant improvement in the primary outcome, the companies report.

However, a prespecified subgroup analysis suggested that patients treated with Wainua as monotherapy experienced fewer primary composite events than those receiving placebo, a finding the companies described as nominally significant. No treatment benefit was observed among patients who were receiving a transthyretin stabilizer at baseline.

Despite missing the primary endpoint, AstraZeneca said Wainua was generally well tolerated, with a safety profile consistent with previous clinical studies.

“The CARDIO-TTRansform trial was designed to examine the role of Wainua, a gene silencer treatment, on top of today's standard of care in reducing recurring cardiovascular events and mortality,” AstraZeneca's executive vice president for BioPharmaceuticals R&D **Sharon Barr** is quoted in a release as saying. “Although the trial did not meet its primary objective, we believe the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients worldwide suffering from this progressive and often fatal condition.”

CARDIO-TTRansform is the largest ATTR-CM clinical trial conducted to date, enrolling 1,432 patients at 130 sites across 20 countries, according to the companies. Participants were randomized to receive either 45 mg of eplontersen or placebo by subcutaneous injection every four weeks.

ATTR-CM is a progressive disease caused by the accumulation of misfolded transthyretin protein in the heart, leading to worsening cardiac function and heart failure. The condition may be hereditary or age-related and is estimated to affect between 300,000 and 500,000 people worldwide.

Wainua is described as an RNA-targeted antisense therapy designed to reduce production of transthyretin protein in the liver. The drug is currently approved in more than 20 countries, including the U.S. and European Union, for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy, but not for ATTR-CM.

AstraZeneca and Ionis say they will conduct additional analyses of the complete dataset to better understand the trial results. Full findings are expected to be presented at the European Society of Cardiology Congress next month.