Status Change

AstraZeneca closes enrollment in Phase 2 test of eplontersen plus ALXN2220 combo

The 326-patient ATTRiumph trial will test whether adding an anti-amyloid antibody to eplontersen clears cardiac amyloid faster than the approved RNA drug alone, with results due in 2029.

By AppliedXLJuly 14, 2026Trial NCT07608354

Executive Summary

AstraZeneca closed enrollment in a Phase 2 trial testing whether adding an antibody to its approved TTR-silencing drug improves exercise capacity in transthyretin amyloid cardiomyopathy beyond what the silencer alone delivers.
The combination strategy follows a monotherapy pivotal trial from the same drug that missed its primary cardiovascular endpoint, raising the bar for what pairing it with an antibody must demonstrate to justify the added complexity.
The trial filled its target enrollment on schedule and its completion timeline moved slightly earlier rather than later, indicating no operational strain behind the status change.
The transthyretin amyloidosis field already has multiple validated mechanisms in Phase 3 and beyond, so this trial's readthrough lies in testing a clearance-plus-silencing combination rather than opening a new mechanistic class.

The trial

The trial, registered as NCT07608354 and named ATTRiumph, moved to Active, not recruiting status on July 14, 2026, after the sponsor reported it had reached its anticipated enrollment of 326 adults with ATTR-CM. The Phase 2, randomized, placebo-controlled study is testing eplontersen given alongside ALXN2220, an antibody, against eplontersen plus placebo. Its primary endpoint is the change from baseline in cardiopulmonary exercise test peak VO2, a measure of exercise capacity, at week 52. The trial's primary completion date sits at February 6, 2029, after the registry moved that date up from February 23, 2029 in mid-June, a 17-day pull-forward rather than a slip. NCT07608354

Probability of Success

Endpoint Met75%

Completes89%

Clinical Significance50%

Regulatory85%

What the combination tests

Eplontersen, marketed as Wainua, degrades TTR messenger RNA to reduce production of the misfolded protein that deposits in the heart. ALXN2220 works by a different mechanism, targeting existing misfolded TTR for clearance, so the combination pairs a production-blocking drug with an amyloid-clearing antibody in the same regimen. That distinction matters because AstraZeneca's own Phase 3 CARDIO-TTRansform trial of eplontersen alone, partnered with Ionis Pharmaceuticals, did not meet its primary composite endpoint of cardiovascular death and recurrent cardiovascular events, a result disclosed July 9, 2026. The Phase 2 combination trial is testing whether adding amyloid clearance to TTR silencing can produce a exercise-capacity benefit that silencing alone, at pivotal scale, did not translate into a positive cardiovascular outcome. NCT07608354

Enrollment and stability

The enrollment closed at exactly its anticipated target of 326 patients, with no increase or reduction recorded against that target. The trial's registry history shows one status change in June from Not yet recruiting to Recruiting, one adjustment to the primary completion date, and now the move to Active, not recruiting, a single amendment per year that reads as a stable protocol rather than a disrupted one. That enrollment pattern and the on-schedule completion date place trial execution outside the concerns that typically accompany an operational update. NCT07608354

The competitive field

Transthyretin amyloid cardiomyopathy already has a validated mechanism landscape: Pfizer's tafamidis is approved as a stabilizer, and TTR-silencing RNA therapies from Alnylam Pharmaceuticals (vutrisiran, patisiran) and Ionis Pharmaceuticals (eplontersen) sit in Phase 3 or later, alongside Intellia Therapeutics' CRISPR-based NTLA-2001. Direct peers sharing eplontersen's mechanism and indication include Ionis's own Phase 3 extension trial of eplontersen (NCT05667493). Against that backdrop, the informative result for this Phase 2 readout is whether adding antibody-based clearance to a silencing backbone moves an objective exercise-capacity measure beyond what RNA silencing alone achieved in the same disease. NCT07608354

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.