– Study missed primary endpoint of composite outcome of cardiovascular (CV) mortality and recurrent CV events; in a pre-specified subgroup analysis, a nominally significant result was observed with eplontersen monotherapy –
– Favorable safety profile consistent with previous results –
CARLSBAD, Calif., July 09, 2026--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) and partner AstraZeneca today announced that the CARDIO-TTRansform Phase 3 trial for eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not meet the primary efficacy endpoint of the composite outcome of cardiovascular (CV) mortality and recurrent CV clinical events up to Week 140 compared with placebo. In this contemporary patient population treated with standard of care, including a majority on a stabilizer, adding eplontersen did not provide a statistically significant benefit.
In a prespecified subgroup analysis of patients treated with eplontersen monotherapy compared to placebo, a nominally significant hazard ratio of 0.71 was observed on the composite outcome of CV mortality and recurrent CV events. In patients who were on stabilizer therapy at baseline, no treatment effect was observed.
In the overall population, multiple secondary, imaging and biomarker analyses favored eplontersen versus placebo. Large and sustained reductions in transthyretin (TTR) were observed, consistent with the silencer class for ATTR. Eplontersen was well tolerated, with a favorable safety profile consistent with previous results.
"We believe these findings reflect the rapidly evolving treatment landscape, in which contemporary ATTR-CM patients are widely treated with stabilizers," said Brett P. Monia, Ph.D., chief executive officer, Ionis. "Although we are disappointed that the study did not meet the primary endpoint, these results have the potential to guide the treatment landscape for ATTR-CM and contribute to advancing future care for patients. We extend our sincere gratitude to the patients, families and investigators whose participation helped progress the science of ATTR-CM treatment."
CARDIO-TTRansform is a Phase 3, multicenter, randomized, double-blinded, placebo-controlled study to evaluate the safety and efficacy of eplontersen compared to placebo in participants with ATTR-CM receiving available standard of care: 57% of patients in each arm received a stabilizer treatment at baseline, and a further 24% in each arm initiated a stabilizer during the trial.
"Ionis continues to be well positioned to create substantial value in both the near and long term, driven primarily by the strength of our wholly owned portfolio," said Monia. "We have multiple successful independent launches underway, including TRYNGOLZA, our first in a prevalent population, and we continue to advance a robust pipeline of potentially transformational medicines. We remain on track to deliver a steady cadence of new medicines to patients and achieve cash flow breakeven by 2028."