AstraZeneca PLC / CSPC Pharmaceutical Group Ltd.

Dyslipidemia and atherosclerotic cardiovascular disease (elevated Lp(a))

64M US cases/yr · $10.0B Lp(a)-lowering class peak analyst consensus · 2020 AstraZeneca-CSPC deal size (USD MM, $100M upfront + $1.92B milestones)

Disease Overview

Lipoprotein(a), or Lp(a), is a genetically determined lipoprotein particle that causes atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis independent of LDL-C. Approximately 20% of the global population — roughly 64 million US adults — has elevated Lp(a) above the 50 mg/dL risk threshold (AHA/ACC guidelines), and there is no approved Lp(a)-lowering therapy. Statins, ezetimibe and PCSK9 inhibitors (evolocumab/Repatha, alirocumab/Praluent) do not meaningfully lower Lp(a); lipoprotein apheresis is the only currently available option and is logistically impractical. The class is validated by Mendelian randomization (lifelong low Lp(a) equals lower CV risk) and by Lp(a)-specific agents in Phase 3: olpasiran (Amgen siRNA), pelacarsen (Novartis/Ionis antisense, HORIZON trial), lepodisiran (Lilly siRNA, ACCLAIM-Lp(a) Phase 3). Oral small molecules that disrupt Lp(a) assembly represent a major convenience and cost advantage over the injectable RNAi/ASO class; the category leader is muvalaplin (Lilly, Phase 2 KRAKEN readout late 2024 showed 65-85% reduction). YS2302018 / AZD0780 (the latter is AZ's PCSK9 inhibitor) combination concept positions AZ as the first to couple oral Lp(a) lowering with oral PCSK9, the two most important lipid-lowering targets beyond statins.

Competitive Landscape

The Lp(a)-lowering category is the next major cardiovascular franchise beyond PCSK9. Injectable RNAi / ASO (late stage): olpasiran (Amgen, siRNA, Phase 3 OCEAN(a)-Outcomes); pelacarsen (Novartis / Ionis, antisense, Phase 3 HORIZON); lepodisiran (Eli Lilly, siRNA, Phase 3 ACCLAIM-Lp(a)); zerlasiran (Silence / Otsuka, siRNA, Phase 2). Oral small molecule Lp(a) disruptors: muvalaplin (Eli Lilly, Phase 2 KRAKEN readout Nov 2024); YS2302018 (CSPC / AstraZeneca, early-stage oral Lp(a) disruptor). Oral PCSK9 (adjacent mechanism): AZD0780 (AstraZeneca, Phase 2 PURSUIT), MK-0616 / enlicitide (Merck, Phase 3). Established injectable PCSK9: evolocumab (Repatha, Amgen); alirocumab (Praluent, Sanofi/Regeneron); inclisiran (Leqvio, Novartis siRNA). The AZD0780 + YS2302018 combination concept positions AstraZeneca at the intersection of the two most contested oral lipid programs, offering a potential dual oral LDL-C and Lp(a) regimen that none of Amgen, Lilly or Novartis currently have in the same package.