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Get filing alertsIonis Phase 3 trial for eplontersen in ATTR-CM fails primary endpoint
Filed July 9, 2026 · Period ending July 9, 2026 · ~1 min read
Key Changes
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CARDIO-TTRansform Phase 3 trial (1,432 patients, largest ATTR-CM study to date) failed to show statistically significant benefit on cardiovascular mortality and recurrent CV events versus placebo at Week 140.
Item 8.01 — Other Events verify on EDGAR → -
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Prespecified subgroup analysis showed nominally significant benefit (hazard ratio 0.71) for eplontersen monotherapy, but no treatment effect in patients already on stabilizer therapy (57% at baseline, 81% total).
Item 8.01 — Other Events verify on EDGAR → -
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Company reaffirmed cash flow breakeven target by 2028 and highlighted ongoing launches including TRYNGOLZA, its first drug in a prevalent population.
Exhibit 99.1 view on EDGAR →
Summary
Ionis disclosed that its Phase 3 CARDIO-TTRansform trial evaluating eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) failed to meet its primary endpoint. The study, the largest ATTR-CM trial to date with 1,432 participants across 20 countries, found no statistically significant benefit when eplontersen was added to standard of care compared to placebo on the composite outcome of cardiovascular mortality and recurrent cardiovascular events through Week 140. The majority of patients (57% in each arm) were already receiving stabilizer therapy at baseline, with an additional 24% initiating stabilizers during the trial.
A prespecified subgroup analysis showed a nominally significant hazard ratio of 0.71 for patients receiving eplontersen as monotherapy, suggesting potential benefit in a narrower patient population not on stabilizers. However, this was not the primary endpoint, and the overall trial failure represents a significant setback for the drug's development in this indication. The company emphasized its broader pipeline strength and reaffirmed its 2028 cash flow breakeven target, pointing to ongoing launches including TRYNGOLZA as drivers of future value.
Section-by-Section Diff
Event · Item 7.01 — Regulation FD Disclosure
Item 7.01 — Regulation FD Disclosure filed; see Key Changes for terms.
Added in current filing · verify on EDGAR →
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
Ionis disclosed that its Phase 3 clinical trial evaluating eplontersen for ATTR-CM failed to achieve statistical significance on the primary endpoint, which measured cardiovascular mortality and recurrent cardiovascular events over 140 weeks versus placebo. This is a setback for the drug candidate in this indication, though the filing does not disclose whether secondary endpoints were met or what next steps the company will take.
Event · Exhibit 99.1
Ionis disclosed that its Phase 3 CARDIO-TTRansform trial of eplontersen for ATTR-CM missed its primary endpoint.
Added in current filing · verify on EDGAR →
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.
Ionis and partner AstraZeneca announced that their Phase 3 trial of eplontersen in ATTR-CM patients failed to meet its primary endpoint. The study evaluated cardiovascular mortality and recurrent cardiovascular events through Week 140, and adding eplontersen to standard of care (which included stabilizer therapy in a majority of patients) did not show a statistically significant benefit versus placebo. This is a setback for the drug's development in this indication.
Added in current filing · verify on EDGAR →
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.
A prespecified subgroup analysis showed a nominally significant benefit (hazard ratio 0.71) for eplontersen monotherapy versus placebo on the composite endpoint. However, in patients already on stabilizer therapy at baseline, no treatment effect was seen. This suggests eplontersen may have benefit when used alone but not when added to stabilizers, reflecting the evolving treatment landscape where most contemporary ATTR-CM patients receive stabilizers.
Added in current filing · view on EDGAR →
CARDIO-TTRansform is a global, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy and safety of eplontersen in adults with wild-type or hereditary ATTR-CM who are receiving available standard of care therapy. As the largest enrolled ATTR-CM trial to date, CARDIO-TTRansform enrolled 1,432 participants across 130 study sites in 20 countries, who were randomized 1:1 to receive eplontersen 45 mg or placebo by subcutaneous injection every four weeks.
The trial was the largest ATTR-CM study to date, enrolling 1,432 participants across 130 sites in 20 countries. Patients were randomized equally to receive eplontersen 45 mg or placebo subcutaneously every four weeks, on top of standard of care. The trial's size and global scope underscore the significance of the negative result.
Added in current filing · verify on EDGAR →
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.
The majority of trial participants (57% in each arm) were already on stabilizer therapy at baseline, and an additional 24% in each arm started stabilizers during the trial. This high rate of stabilizer use reflects current standard of care and may explain why adding eplontersen did not show benefit in the overall population, as the company attributes the negative result to the evolving treatment landscape.
Added in current filing · view on EDGAR →
“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.”
Despite the trial failure, CEO Brett Monia emphasized that Ionis remains well positioned with its wholly owned portfolio, including ongoing launches such as TRYNGOLZA (its first drug in a prevalent population) and a robust pipeline. The company reaffirmed its target to achieve cash flow breakeven by 2028, signaling confidence in its broader business despite this setback.
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Figures/quotes linked to EDGAR · Narrative written by AI · Jul 10, 2026 · How we verify