Does olpasiran (AMG 890, GalNAc-siRNA, hepatic apo(a) knockdown, ~95% Lp(a) lowering) meet its primary endpoint — reduction in coronary MACE (CHD death, MI, or urgent coronary revascularization) vs placebo — in the Lp(a) ≥200 nmol/L ASCVD population of OCEAN(a)-Outcomes?

70% likely to meet · raimo

target Lp(a) particle + LPA (apolipoprotein(a)) · moa siRNA (GalNAc-conjugated); hepatic APO(a) knockdown; ~95% Lp(a) lowering · failure mode biomarker lowered without proportional outcome benefit; lifelong-genetic causal effect fails to translate to 5-yr pharmacologic exposure (low translation fraction tau)

1. premise Same causal target as pelacarsen: 5.8% lower CHD per 10 mg/dL genetically lower Lp(a) (genetic log-HR ~= -0.00597/mg/dL). Olpasiran and pelacarsen are two molecules testing one hypothesis. https://pubmed.ncbi.nlm.nih.gov/29926099/
2. premise Olpasiran lowers Lp(a) ~95% (GalNAc-siRNA, q12wk) on a higher-Lp(a) population (>=200 nmol/L ~ >=93 mg/dL) than HORIZON's >=70 mg/dL - a larger absolute mg/dL reduction (the bigger hammer). https://clinicaltrials.gov/study/NCT05581303
3. premise OCEAN(a)-Outcomes is event-driven, ~7,297 ASCVD patients, primary completion Dec 2026; primary is coronary 3-point MACE (CHD death, MI, urgent coronary revascularization, no stroke) - a coronary-focused endpoint where Lp(a)'s causal signal is strongest. https://clinicaltrials.gov/study/NCT05581303
4. inference Read-across from the pelacarsen MR->power bridge: larger absolute reduction + coronary-only endpoint both modestly raise the predicted effect vs HORIZON. But this is the SAME translation-fraction (tau) bet - pelacarsen and olpasiran are correlated, not independent: if tau~0 both miss, if Lp(a) lowering translates both likely hit. https://pubmed.ncbi.nlm.nih.gov/29926099/ https://pubmed.ncbi.nlm.nih.gov/31017618/
5. prediction Olpasiran meets its primary coronary-MACE endpoint vs placebo. p(met)=0.70, slightly above pelacarsen (bigger absolute reduction, cleaner coronary endpoint), capped by the same first-in-class tau tail and correlated with the pelacarsen call. Caveat: OCEAN(a) event count not pulled, so power is not independently computed - p anchors to the pelacarsen bridge adjusted qualitatively.

Evidence: https://pubmed.ncbi.nlm.nih.gov/29926099/, https://pubmed.ncbi.nlm.nih.gov/31017618/, https://clinicaltrials.gov/study/NCT05581303