ESC 2026: Five stories that mattered in Munich

1. Cytokinetics: first-ever targeted therapy benefit in nonobstructive HCM

The news was so big that one section wasn’t enough. During one of Friday’s Hot Line sessions and a Saturday’s Late Breaking Clinical Trial session, Cytokinetics shared detailed data from its phase 3 trial for Myqorzo (aficamten), a cardiac myosin inhibitor, in non-obstructive hypertrophic cardiomyopathy (nHCM). The results were also published simultaneously in The New England Journal of Medicine.

ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM) met its dual primary endpoints: aficamten delivered a +3-point KCCQ-CSS (a patient-reported quality-of-life measure for heart failure) advantage over placebo at 36 weeks, rising to +7 points at 72 weeks, plus objective exercise capacity gains (measured by peak oxygen uptake during exercise, pVO2). This sets up a label expansion from obstructive HCM (U.S. FDA approved in December 2025) into nHCM — a patient population of roughly 1 in 200–500 people with currently no approved drugs.

2. Bristol Myers Squibb: another cardiac-myosin-inhibitor with good news

In a late-breaker presentation, BMS shared on Saturday its phase 3 long-term results for Cytokinetics’ Myqorzo competitor Camzyos (mavacamten). With its 5-year data, BMS claims EXPLORER-LTE trial to be “the longest-running clinical development experience for a cardiac myosin inhibitor (CMI) in symptomatic obstructive HCM.”

This latest data confirmed the sustained, clinically meaningful effects of Camzyos in patients with symptomatic obstructive HCM, with no new safety signals beyond those identified in the primary EXPLORER-HCM study.

For now, the rivalry between the two cardiac myosin inhibitors is confined to obstructive HCM, where Camzyos is already established as a standard of care. Its sibling failure in nHCM — mavacamten missed the primary endpoint in a phase 3 trial last year — leaves the nonobstructive field open to Myqorzo for the time being. BMS isn’t conceding, though: it plans to start a new nHCM trial of Camzyos in a more targeted population before the end of the year.

3.  Ionis + AstraZeneca: post-mortem RNAi analysis and speculations

After announcing the trial failure in early July, one of the most expected presentations at the ESC was the detailed data of Ionis and AZ’s Wainua (eplontersen) gene silencer in preventing cardiovascular death or events (such as heart attack and stroke) in individuals with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).

In the first Hot Line session on Friday morning, the data deep dive suggested background Pfizer’s tafamidis (as Vyndamax and Vyndaqel) use could have muddied the signal. Only a minority of individuals in the CARDIO-TTRansform trial were treated with Wainua as monotherapy.

Eplontersen is a gene silencer, and tafamidis is a stabilizer of the misfolding TTR protein. While planning the trial, everyone believed that adding a TTR silencer to an already working stabilizer would improve the outcomes. But the shared results proved them wrong. Since eplontersen indeed reduced the levels of circulating serum TTR as intended, future analysis (and probably more clinical trials) could determine whether eplontersen can work as a monotherapy for ATTR-CM.

4. Arrowhead: an siRNA that worked in severe hypertriglyceridemia

On one of Sunday afternoon’s Hot Line sessions, Arrowhead presented the full 12-month data from its pivotal Phase 3 SHASTA-3 and SHASTA-4 trials of plozasiran (marketed as Redemplo for familial chylomicronemia syndrome) in adults with severe hypertriglyceridemia (sHTG). Both trials met their primary and all prespecified secondary endpoints.

Plozasiran is a small interfering RNA (siRNA) that silences APOC3, the gene encoding apolipoprotein C-III, a protein that normally inhibits triglyceride clearance from the bloodstream.

The headline numbers were striking: median triglyceride reductions of 79% in SHASTA-3 and 81% in SHASTA-4 at 12 months (p<0.0001 for each).

But it was the pancreatitis data that drew the most attention. In a prespecified pooled analysis, plozasiran cut acute pancreatitis events by 78% across the overall sHTG population. Among patients with a prior history of pancreatitis — the highest-risk subgroup — the reduction approached 100%.

While the drug was already approved earlier this year for familial chylomicronemia syndrome (FCS) in Australia, these pivotal results position Arrowhead to file a supplemental NDA with the U.S. FDA before the end of 2026, and the company has already purchased a Priority Review Voucher to accelerate the process.

5. For once, GLP-1 wasn’t in the headlines. But…

The same Friday that ESC started, Eli Lilly announced the FDA approval of Mounjaro (tirzepatide), its dual GIP and GLP-1 hormone receptor agonist, to reduce cardiovascular risk in adults with type 2 diabetes; this includes cardiovascular death, non-fatal heart attack, and non-fatal stroke.

The announcement wasn’t shared at the conference, and no other big news regarding GLP-1 drugs was shared. However, GLP-1 appeared in the 2026 ESC Heart Failure guidelines.

It was announced that semaglutide and tirzepatide received Class IIa recommendations for Heart Failure with Preserved Ejection Fraction (HFpEF) with obesity (BMI ≥30), cementing the GLP‑1 revolution in cardiology.