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• The P-II (ALPACA) trial assessed lepodisiran (16, 96, or 400mg) vs PBO for ~18mos. in 320 pts, who were dosed at baseline & day 180, with an additional arm receiving 400mg at baseline & PBO at day 180; P-III [ACCLAIM-Lp(a)] trial enrollment is ongoing
• Trial met its 1EP, with 400mg reducing Lp(a) by 93.9% over 60-180 days; 16 mg & 96 mg showed 40.8% & 75.2% reductions, respectively; impact of additional lepodisiran doses remain unknown
• 2EPs showed 400mg (dosed twice) reduced Lp(a) by 94.8% (day 30-360), sustained at 91% at ~1yr. & 74.2% at ~1.5yrs., with ApoB reductions of 14.1% (day 60) & 13.7% (day 180), maintained through day 540; data was presented at ACC 2025 & published in The NEJM

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