Ionis Pharmaceuticals Inc. (NASDAQ:IONS) and partner AstraZeneca Plc (NYSE:AZN) on Thursday said their Phase 3 CARDIO-TTRansform study of eplontersen for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) failed to meet its primary efficacy endpoint.
In patients receiving contemporary standard of care, including a majority treated with a transthyretin stabilizer, adding eplontersen did not significantly reduce the combined risk of cardiovascular mortality and recurrent cardiovascular clinical events through Week 140 versus placebo.
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.
Subgroup Analysis And Secondary Endpoints
ATTR-CM is caused by misfolded transthyretin (TTR) proteins that build up in the heart, stiffening the heart muscle, leading to heart failure.
Although the primary endpoint was not met in the overall study population, a prespecified subgroup analysis showed a nominally significant hazard ratio of 0.71 for the composite endpoint in patients receiving eplontersen as monotherapy compared with placebo.
By contrast, researchers reported no treatment effect among patients who were already receiving stabilizer therapy at baseline.
The companies also said several secondary endpoints, including imaging and biomarker analyses, favored eplontersen over placebo in the overall study population. The treatment produced large and sustained reductions in transthyretin (TTR), consistent with the expected effects of the silencer drug class.
Safety Profile Remains Consistent
Ionis and AstraZeneca said eplontersen was well-tolerated throughout the study, with a safety profile consistent with findings from previous clinical trials.
The companies added that they will continue analyzing the complete CARDIO-TTRansform data set. Full results are scheduled to be presented to the scientific community at the European Society of Cardiology Congress in August 2026.
“We believe these findings reflect the rapidly evolving treatment landscape, in which contemporary ATTR-CM patients are widely treated with stabilizers,” said Brett Monia, CEO, Ionis.
“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.”
Price Action: AstraZeneca shares were down 8.09% at $173.97, and Ionis Pharmaceuticals shares were down 21.87% at $65.98 during premarket trading on Thursday, according to Benzinga Pro data.
Image via Shutterstock
Recent Comments