Eplontersen Misses Primary Endpoint in ATTR-CM Trial, Clouding Alnylam RNAi Outlook at ESC
Eplontersen’s failure to meet its primary cardiovascular endpoint at ESC 2026 raises questions about the ability of TTR-lowering agents to improve hard outcomes in ATTR-CM. Alnylam’s RNAi candidates now carry additional clinical and commercial risk. Next trials must deliver clear mortality or hospitalization reductions within defined timeframes to restore confidence.
Regulatory and investor focus will now shift to upcoming vutrisiran cardiovascular outcome data expected in late 2026. If those trials meet endpoints with hazard ratios below 0.75, Alnylam could still secure expanded labeling; failure would likely compress valuation and delay nucresiran advancement. Payers are already conditioning broader RNAi adoption on demonstration of mortality benefit beyond surrogate TTR lowering.
VITALIS: Alnylam’s vutrisiran phase 3 cardiovascular outcomes trial will report a hazard ratio below 0.75 for the primary endpoint by December 2027.
Sources (3)
- [1]Primary Source(https://www.statnews.com/2026/08/27/alnylam-amvuttra-nucresiran-heart-drugs-esc/)
- [2]Supporting Source(https://www.nejm.org/doi/full/10.1056/NEJMoa2305434)
- [3]Supporting Source(https://www.escardio.org/Congresses/ESC-Congress-2026)