Goldman Sachs Americas Healthcare: Biotechnology — KOL Discussions Frame Key ESC Data

During the ESC congress, Goldman Sachs interviewed several cardiology key opinion leaders on three Phase 3 readouts: AZN/IONS's Wainua in ATTR cardiomyopathy (CARDIO-TTRansform), Cytokinetics' aficamten in non-obstructive hypertrophic cardiomyopathy (ACACIA-HCM), and Arrowhead's SHASTA-3/4 in severe hypertriglyceridemia, due for release on Sunday. CARDIO-TTRansform missed its primary endpoint (rate ratio 0.89, p=0.28): Wainua monotherapy showed benefit (HR 0.71), but the combination with a stabilizer was inferior to stabilizer alone (HR 1.14); all-cause mortality HR was 0.77 versus 0.88 for cardiovascular death. KOLs do not view this as a class failure. First-line monotherapy prescribing (Amvuttra share 30–60%) should be unchanged, combination use stays limited, and payers are expected to enforce step-through once generic tafamidis launches, with combination relevance deferred until Pfizer's tafamidis patents expire in the 2030s. For ACACIA-HCM, investor concerns about modest efficacy magnitudes (KCCQ +3; pVO2 +0.67) and limited heart-failure events were outweighed by expectations of broad adoption: >70% symptom response, 53% of patients achieving ≥3 efficacy domains, NT-proBNP 1.7, septal e' 4.0, symptom improvement 5.5, and new-onset atrial fibrillation no different from placebo. KOLs see Arrowhead's Redemplo as broadly similar to Tryngolza (~85% consistency in high-risk patients), with prescribing driven by out-of-pocket costs and safety details. Ratings unchanged: ALNY Buy, PT $536; CYTK Buy, PT $105; IONS Neutral, PT $69.