Category: Cardiometabolic
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Does lowering Lp(a) actually cut cardiovascular events? The outcome trials — HORIZON, OCEAN(a) and ACCLAIM — and why the first readout is still not in
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, and not medical advice. The 30-second version What. Earlier parts of this series established that Lp(a) is causal (Mendelian randomization), genetically fixed, and now pharmacologically lowerable by 80–90%+ with siRNA/ASO/oral agents. But biomarker…
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Lowering Lp(a) is a solved problem — the RNA pipeline now competes on durability, not on depth
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, not medical advice. The 30-second version What. Four nucleic-acid drugs that shut down hepatic apo(a) production — one antisense oligonucleotide (pelacarsen) and three siRNAs (olpasiran, lepodisiran, zerlasiran) — have already saturated the depth…
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The clinical cost behind the GLP-1 headline — reading lean-mass loss, discontinuation, rebound, and safety signals by evidence tier
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, and not medical advice. The 30-second version What. The GLP-1/GIP headline of −15 to −20% body weight comes with clinical costs: loss of lean (fat-free) mass, real-world discontinuation (roughly 50%+ within a year),…
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The GLP-1 commercial map (Part 3): not “who wins” but “who gets access” — the Novo–Lilly duopoly and the access bottleneck
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice. The 30-second version What. In the 2025–26 GLP-1 commercial map, US prescription share has flipped: Lilly (tirzepatide) overtook Novo (semaglutide) — roughly 57%+ vs 43% of US scripts as of Q3 2025 (press…
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The next-generation obesity pipeline: from “how much you lose” to “at what cost”
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, not medical advice. The 30-second version What. The next-generation obesity drugs push weight-loss efficacy along three vectors: triple agonists (retatrutide), oral small molecules (orforglipron), and amylin combinations (CagriSema). At the top end, retatrutide’s…
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Do incretins move hard outcomes in CKM, not just weight? A close read of SELECT, FLOW and SUMMIT
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, and not medical advice. The 30-second version What. GLP-1 / incretin agents lowered hard cardiovascular (SELECT) and kidney (FLOW) outcomes. In SELECT’s pre-specified analysis, roughly two-thirds of the cardiovascular benefit appeared independent of…
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ATTR-CM Part 3 — gene editing (nex-z): a single, permanent TTR knockout buys durability by genome permanence, but the real bottleneck is the asymmetric safety risk that irreversibility creates
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, not medical advice. All reduction and knockdown figures are attributed to the sponsoring trial or company; nex-z Phase 1 numbers are Intellia investor/conference data (AHA 2025-11), company presentations rather than peer-reviewed data. Safety…
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Lp(a) lowering is already a gold rush — but every road runs to one readout, and the events have not been read
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, not medical advice. The 30-second version What. Lipoprotein(a) lowering is already a mature commercial field: three injectable siRNA/ASO agents are in large cardiovascular-outcome Phase 3 trials at roughly 90%+ Lp(a) reduction, an oral…
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Oral muvalaplin and the measurement problem — why half of Lp(a)’s “efficacy gap” may be the ruler, not the drug
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, not medical advice. The 30-second version What. Muvalaplin (Eli Lilly, LY3473329) is the first oral, once-daily small molecule that lowers lipoprotein(a) — it blocks assembly of the Lp(a) particle rather than shutting off…
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Lp(a) is causal — so how much do you have to lower it? Mendelian randomization, epidemiology and the 2026 guideline turn
Evidence-first notes on bioscience and deep tech, at the edge of the lab and the market. Information only — not investment advice, and not medical advice. The 30-second version What. The causal case for lipoprotein(a), Lp(a), as a driver of atherosclerotic cardiovascular disease is one of the strongest genetic cases in cardiology — Mendelian randomization…
