Key Takeaways:
Ionis Pharmaceuticals and AstraZeneca's eplontersen failed to meet the primary endpoint in a 1,432-patient Phase 3 trial for transthyretin-mediated amyloid cardiomyopathy, the companies said July 9.
"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," Brett P. Monia, chief executive officer of Ionis, said.
The CARDIO-TTRansform study tested eplontersen against placebo in adults with ATTR-CM who were receiving standard of care. Fifty-seven percent of patients in each arm were on a stabilizer at baseline, with an additional 24 percent starting one during the trial. In the overall population, adding eplontersen to standard of care did not provide a statistically significant benefit on the composite of cardiovascular mortality and recurrent CV events through Week 140. A prespecified subgroup analysis of patients on eplontersen monotherapy showed a nominally significant hazard ratio of 0.71 versus placebo, while no treatment effect was observed in patients on stabilizer therapy.
The failure represents a setback for Ionis and AstraZeneca, which jointly developed eplontersen. The drug is already approved as WAINUA for hereditary ATTR polyneuropathy in more than 20 countries, but the ATTR-CM indication represented a larger market opportunity with an estimated 300,000 to 500,000 patients worldwide. Levi & Korsinsky announced a pending securities investigation into AstraZeneca following the disclosure.
Large and sustained reductions in transthyretin protein were observed, consistent with the TTR silencer class. Eplontersen was well tolerated with a favorable safety profile, the companies said. Multiple secondary, imaging and biomarker analyses favored eplontersen versus placebo in the overall population.
The results will be presented at the European Society of Cardiology Congress in August 2026. Ionis and AstraZeneca said they will continue analyzing the full data set.
The trial outcome raises questions about the role of TTR silencers in ATTR-CM patients already on stabilizer therapy, potentially reshaping the treatment paradigm. Investors will watch the ESC Congress presentation in August for further data and any impact on eplontersen's commercial prospects in the broader ATTR-CM market.
This article is for informational purposes only and does not constitute investment advice.
