AstraZeneca (NASDAQ: AZN) and Ionis Pharmaceuticals (NASDAQ: IONS) presented Sunday August 30, 2026 at ESC Congress 2026 Munich the detailed subgroup analyses from the Phase 3 CARDIO-TTRansform trial of Wainua (eplontersen, an antisense oligonucleotide targeting transthyretin) in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). CARDIO-TTRansform did not meet its primary composite endpoint (cardiovascular mortality plus recurrent CV events through 140 weeks) versus placebo. In the prespecified subgroup analysis, patients receiving eplontersen monotherapy achieved a nominally significant hazard ratio of 0.71 versus placebo, while patients on background TTR stabilizer therapy (tafamidis, Vyndaqel/Vyndamax) at baseline showed no treatment effect. The read-out complicates the silencer-plus-stabilizer commercial approach in ATTR-CM that Alnylam's HELIOS-B trial of vutrisiran validated with 28.2% mortality reduction and 32.8% CV event reduction on background tafamidis. AstraZeneca and Ionis will analyze the full dataset to inform next steps in the CARDIO-TTRansform program.
Alnylam Pharmaceuticals (NASDAQ: ALNY) shares extended a roughly 30% selloff since the Thursday July 30, 2026 Q2 2026 earnings report, losing approximately $12 billion in market capitalization over the intervening days. The selloff reflects two consecutive negative signals for the RNAi therapeutics leader: the July 30 Amvuttra (vutrisiran, the TTR-directed siRNA that crossed $1 billion in quarterly revenue for the first time at $1.012 billion) full-year 2026 TTR product sales guidance cut to $4.2-4.5 billion (down from prior higher expectations) to reflect normalized second-line volume after the initial pent-up demand from patients waiting for a new therapy, combined with the July AstraZeneca-Ionis eplontersen (Wainua, antisense oligonucleotide) Phase 3 CARDIO-TTRansform study setback that complicates the broader ATTR-CM competitive landscape. The Amvuttra franchise has been positioned as the primary siRNA alternative to Pfizer's Vyndaqel/Vyndamax (tafamidis, small-molecule TTR stabilizer) and BridgeBio's Attruby (acoramidis, next-generation TTR stabilizer). Alnylam presents full eplontersen study data at a late-August medical meeting; analysts flagged the timing as a continued overhang until the presentation clarifies the ATTR-CM segment dynamics. Analyst commentary described the combination as a 'one-two punch' for the company.
AstraZeneca and Ionis Pharmaceuticals announced Thursday July 9, 2026 that the Phase 3 CARDIO-TTRansform trial of Wainua (eplontersen) did not meet its primary efficacy endpoint in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The trial enrolled over 1,400 patients and was the largest Phase 3 study conducted in the ATTR-CM population to date; the primary endpoint was a composite of cardiovascular mortality and recurrent CV clinical events through 140 weeks compared with placebo. Prespecified subgroup analyses showed nominally significant reductions in composite events with eplontersen monotherapy versus placebo, while patients also receiving a baseline TTR stabilizer showed no incremental effect. Eplontersen is an antisense oligonucleotide (a nucleic-acid therapeutic modality distinct from peptides but adjacent in the metabolic-and-cardiovascular therapeutic territory this site tracks); the drug is already FDA-approved as Wainua for hereditary transthyretin amyloidosis polyneuropathy. Full CARDIO-TTRansform results will be presented at the European Society of Cardiology (ESC) Congress in August 2026. AstraZeneca and Ionis shares fell on the readout.