# Eli Lilly's One-Shot Cholesterol Therapy Hits 88% PCSK9 Reduction in Phase 1, Gets Published in NEJM **Source:** https://glitchwire.com/news/eli-lillys-one-shot-cholesterol-therapy-hits-88-pcsk9-reduction-in-phase-1-gets/ **Published:** 2026-05-25T23:59:27.073Z **Author:** Science Desk ยท Glitchwire **Categories:** Science, Tech ## Summary VERVE-102, a base-editing treatment that inactivates the PCSK9 gene with a single infusion, showed durable LDL reductions of up to 62% in patients at high cardiovascular risk. ## Article A single intravenous infusion of Eli Lilly's VERVE-102 reduced circulating PCSK9 protein by up to 88% and lowered LDL cholesterol by as much as 62% in a Phase 1b trial, with effects persisting for at least 18 months. The results, [announced today](https://www.prnewswire.com/news-releases/a-single-dose-of-lillys-pcsk9-base-editor-verve-102-reduced-pcsk9-by-up-to-88-and-ldl-c-by-up-to-62-with-durable-effects-supporting-its-potential-as-a-one-time-treatment-for-hypercholesterolemia-302780172.html) at the European Atherosclerosis Society Congress and simultaneously published in *The New England Journal of Medicine*, offer the strongest clinical evidence yet that a permanent gene edit could replace decades of chronic cholesterol management. ## What the Trial Showed The Heart-2 trial enrolled 35 adults with heterozygous familial hypercholesterolemia or premature coronary artery disease across six escalating dose cohorts. These are patients who, despite maximal tolerated statin therapy, remain at elevated cardiovascular risk due to stubbornly high LDL levels. At the highest tested dose of 1.0 mg/kg, PCSK9 dropped 88% and LDL cholesterol fell 62%. Lower doses produced smaller but still meaningful reductions, with the dose-response relationship holding across all cohorts. More importantly, the reductions didn't fade. Some participants have now been followed for 18 months with sustained lowering. The therapy was well tolerated. There were no dose-limiting toxicities and no treatment-related serious adverse events. The main side effects were low-grade infusion-related reactions and fatigue. Critically, there were no clinically significant changes in liver enzymes, bilirubin, or platelet counts at any dose level. ## Why This Matters Existing PCSK9-targeting drugs like Amgen's Repatha and Novartis's Leqvio work well when patients take them. The problem is that many don't. Injections every two weeks or twice-yearly appointments fall off quickly outside clinical trial conditions. Real-world adherence data consistently shows that actual LDL reductions lag far behind what pivotal studies promise. VERVE-102 offers a fundamentally different proposition: a single infusion that permanently edits the PCSK9 gene in liver cells, creating a stop codon that halts production of the protein. The therapy uses an adenine base editor delivered via a proprietary lipid nanoparticle that targets hepatocytes through either the LDL receptor or the asialoglycoprotein receptor. Because heterozygous familial hypercholesterolemia often involves defective LDL receptors, that dual pathway is clinically significant. Verve developed VERVE-102 after its predecessor, VERVE-101, caused liver enzyme elevations and low platelet counts in some patients. The company attributed those issues to the lipid nanoparticle delivery system and redesigned it for the follow-on candidate. The Heart-2 safety profile vindicates that decision. ## Lilly's Bet Eli Lilly [acquired Verve Therapeutics](https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-verve-therapeutics-advance-one-time-treatments) last year for approximately $1.3 billion, including contingent payments. The deal gave Lilly not just VERVE-102 but an entire pipeline of cardiovascular gene-editing programs, including therapies targeting ANGPTL3 and lipoprotein(a). The FDA has granted VERVE-102 Fast Track designation for hyperlipidemia in patients at high cardiovascular risk. Lilly says it plans to begin enrolling a Phase 2 study by the end of this year. Heterozygous familial hypercholesterolemia affects roughly 1 in 250 people, and coronary artery disease remains a leading cause of death worldwide, affecting more than 300 million people. The harder question is pricing. A one-time gene therapy that replaces decades of chronic medication will face intense scrutiny from payers. The value proposition is clear in theory: a permanent fix should cost less than a lifetime of biweekly injections. Whether insurers agree, and whether [the biopharma industry's](/news/edison-scientifics-incyte-deal-shows-what-ai-native-biopharma-actually-looks-lik/) track record on gene therapy pricing inspires confidence, is another matter entirely. For now, the data do what Phase 1 data are supposed to do: establish proof of concept and justify moving forward. Whether VERVE-102 becomes the first approved [gene-editing therapy](/news/colossal-biosciences-hatches-chickens-from-artificial-eggs-unlocking-a-new-path/) for cardiovascular disease depends on trials that haven't started yet. --- **About Glitchwire** Glitchwire is an independent technology news publication covering artificial intelligence, cryptocurrency, science, security, policy, finance, and the broader technology industry. 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