--- title: "Muvalaplin: The First Lp(a)-Lowering Pill — an Oral Drug That Cut Lipoprotein(a) by up to 86% (August 9, 2026) | PepTracker Pro Blog" description: "About one in five people inherit high lipoprotein(a) — a genetic driver of heart attacks and strokes that statins and PCSK9 inhibitors can't touch, and that every advanced treatment so far has required an injection to lower. Muvalaplin, an oral small molecule from Eli Lilly, breaks that pattern: a once-daily pill that blocks Lp(a) from ever assembling, cutting it by up to 86% in the Phase 2 KRAKEN trial. Here's how it works, what KRAKEN showed, and why its Phase 3 MOVE-Lp(a) outcomes trial matters." lang: en json-ld: | [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "Article", "headline": "Muvalaplin: The First Lp(a)-Lowering Pill — an Oral Drug That Cut Lipoprotein(a) by up to 86% (August 9, 2026)", "description": "About one in five people inherit high lipoprotein(a) — a genetic driver of heart attacks and strokes that statins and PCSK9 inhibitors can't touch, and that every advanced treatment so far has required an injection to lower. Muvalaplin, an oral small molecule from Eli Lilly, breaks that pattern: a once-daily pill that blocks Lp(a) from ever assembling, cutting it by up to 86% in the Phase 2 KRAKEN trial. Here's how it works, what KRAKEN showed, and why its Phase 3 MOVE-Lp(a) outcomes trial matters.", "datePublished": "2026-08-09", "dateModified": "2026-08-09", "author": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "publisher": { "@type": "Organization", "name": "PepTracker Pro", "logo": { "@type": "ImageObject", "url": "https://peptrackerpro.com/favicon.png" } }, "mainEntityOfPage": { "@type": "WebPage", "@id": "https://peptrackerpro.com/blog/muvalaplin-lilly-kraken-oral-small-molecule-lp-a-lipoprotein-a-apolipoprotein-a-apob-formation-inhibitor-ly3473329-move-lp-a-cardiovascular-outcomes-august-9-2026" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Blog", "item": "https://peptrackerpro.com/blog" }, { "@type": "ListItem", "position": 3, "name": "Muvalaplin: The First Lp(a)-Lowering Pill — an Oral Drug That Cut Lipoprotein(a) by up to 86% (August 9, 2026)", "item": "https://peptrackerpro.com/blog/muvalaplin-lilly-kraken-oral-small-molecule-lp-a-lipoprotein-a-apolipoprotein-a-apob-formation-inhibitor-ly3473329-move-lp-a-cardiovascular-outcomes-august-9-2026" } ] } ] --- [Skip to main content](#main) **Educational information only.** This site does not provide medical advice. [Read full disclaimer](/disclaimer) [PepTracker Pro](/) [Home](/)[Peptides](/peptides)[Compare](/compare)[Glossary](/glossary)[Blog](/blog)[Calculators](/calculators)[Start Here](/start) [Open the App](https://app.peptrackerpro.com) [Blog](/blog)/ Muvalaplin: The First Lp(a)-Lowering Pill — an Oral Drug That Cut Lipoprotein(a) by up to 86% (August 9, 2026) Research & Compounds Research & Compounds # Muvalaplin: The First Lp(a)-Lowering Pill — an Oral Drug That Cut Lipoprotein(a) by up to 86% (August 9, 2026) PepTracker Pro Research Team August 9, 2026 7 min read ## Table of Contents - [The risk factor genetics deal you at birth](#section-0) - [What muvalaplin is](#section-1) - [How it works: blocking the handshake instead of silencing the gene](#section-2) - [What KRAKEN showed](#section-3) - [A measurement twist worth knowing](#section-4) - [Why the Phase 3 outcomes trial matters](#section-5) - [How it compares with the rest of the class](#section-6) - [The bottom line](#section-7) ## The risk factor genetics deal you at birth Lipoprotein(a) — written Lp(a) and spoken 'L-P-little-a' — is one of the most important cardiovascular risk factors most people have never heard of. Roughly one in five people worldwide inherit high levels, and it is a causal driver of heart attack, stroke, peripheral artery disease, and calcific aortic valve stenosis. Your Lp(a) is set almost entirely by your genes. It barely moves with diet, exercise, or weight loss, and the cholesterol drugs most people know — statins and even the powerful PCSK9 inhibitors — do little or nothing to it. A wave of gene-silencing injections (the siRNAs olpasiran, lepodisiran, and zerlasiran and the antisense oligonucleotide pelacarsen) is trying to change that. Muvalaplin is the odd one out — and the most convenient — because it is a pill. ## What muvalaplin is Muvalaplin — developed by Eli Lilly and previously known as LY3473329 — is an investigational once-daily oral small molecule. It is not a peptide, an siRNA, or an antisense drug. It is the first oral agent of any kind designed specifically to lower Lp(a), and as of 2026 it is the only Lp(a)-lowering drug that is both oral and already enrolling a large Phase 3 cardiovascular outcomes trial. Like the rest of the class, it is investigational and not approved anywhere; it is a prescription clinical-stage medicine, not a supplement or research chemical. ## How it works: blocking the handshake instead of silencing the gene Here is the key difference from every other advanced Lp(a) drug. The injectable therapies work inside liver cells to shut off the LPA gene, so the liver makes less apolipoprotein(a) \[apo(a)\]. Muvalaplin never touches the gene. An Lp(a) particle is built when apo(a) latches onto the apolipoprotein B (apoB) of an LDL-like particle — a molecular handshake. Muvalaplin is a multivalent (trimeric) small molecule that binds the kringle IV domains of apo(a) and blocks that first apo(a)–apoB handshake, so the Lp(a) particle is simply never assembled. Stopping the build, rather than cutting off the supply of one part, is what lets a small-molecule pill do a job that otherwise takes a gene-silencing injection. ## What KRAKEN showed The Phase 2 KRAKEN trial (NCT05563246) enrolled 233 adults with Lp(a) of 175 nmol/L or higher and high cardiovascular risk (established atherosclerotic disease, diabetes, or familial hypercholesterolemia) and randomized them to muvalaplin 10 mg, 60 mg, or 240 mg once daily or placebo. At 12 weeks, muvalaplin produced placebo-adjusted Lp(a) reductions of 47.6% at 10 mg, 81.7% at 60 mg, and 85.8% at 240 mg — up to roughly 86%. The two higher doses also significantly lowered apoB, a broader marker of atherogenic particles. The drug was well tolerated. Results were presented as a late-breaker at the American Heart Association 2024 Scientific Sessions on November 18, 2024, by Stephen Nicholls, and published simultaneously in JAMA. An earlier first-in-human Phase 1 trial in 114 healthy adults, published in JAMA in 2023, had already shown up to about 65% Lp(a) lowering over two weeks of daily dosing with no tolerability concerns. ## A measurement twist worth knowing Muvalaplin created an unusual problem for the lab. Because it works by binding apo(a) and forming apo(a)-containing complexes, conventional Lp(a) blood tests can misread how much Lp(a) is actually left. To measure its effect accurately, KRAKEN used a novel 'intact Lp(a)' assay that counts only fully assembled particles, alongside a standard test. It is a reminder that a drug's mechanism can outrun the tools used to measure it, and it is something clinicians will have to keep in mind if muvalaplin ever reaches practice. ## Why the Phase 3 outcomes trial matters Lowering Lp(a) is not the same as preventing heart attacks — that is the field's central, still-unproven hypothesis, and it can only be answered by a large cardiovascular outcomes trial. Eli Lilly has advanced muvalaplin into exactly that: the Phase 3 MOVE-Lp(a) trial (NCT07157774), enrolling roughly 10,450 adults with elevated Lp(a) who have had, or are at high risk of, an atherosclerotic cardiovascular event, testing whether the pill reduces major adverse cardiovascular events. It is enrolling as of 2025 with results expected later this decade. That places muvalaplin alongside pelacarsen's Lp(a)HORIZON, olpasiran's OCEAN(a)-Outcomes, and lepodisiran's ACCLAIM-Lp(a) as one of the pivotal tests of the whole class — and the only oral entrant among them, at a time when zerlasiran's own Phase 3 is on hold pending a development partner. ## How it compares with the rest of the class All five leading Lp(a)-lowering drugs aim at the same target but differ in how and how often they are given. Pelacarsen (Ionis/Novartis) is a monthly antisense oligonucleotide injection; olpasiran (Amgen) is an every-12-weeks siRNA injection; lepodisiran (Eli Lilly) is a long-duration siRNA injection dosed as infrequently as once or twice a year; zerlasiran (Silence) is an siRNA injection given every 16–24 weeks. Muvalaplin (Eli Lilly) is the outlier: a once-daily oral pill that blocks Lp(a) assembly rather than silencing the LPA gene. Its trade-off is daily dosing versus the injectables' convenience of a shot every few months — but for many people, a pill is far easier to start and stay on than an injection. ## The bottom line Muvalaplin is an investigational, once-daily oral small molecule that blocks the apo(a)–apoB interaction to stop lipoprotein(a) particles from forming, and it cut Lp(a) by up to about 86% in the well-conducted Phase 2 KRAKEN trial published in JAMA. It is the first oral Lp(a)-lowering agent, it is not approved anywhere, and — unlike statins or PCSK9 inhibitors — it targets Lp(a) specifically. Its biggest open question is the same one facing the entire class: not whether it lowers Lp(a) (it clearly does) but whether that lowering prevents heart attacks and strokes. Muvalaplin's advantage is that it is already in the large Phase 3 MOVE-Lp(a) outcomes trial designed to find out — and it is the only one of the leading Lp(a) drugs you would take as a pill. Ready to track your peptide research? [Open PepTracker Pro](https://app.peptrackerpro.com) PepTracker Pro Research Team The PepTracker Pro Research Team is an editorial group of science writers, pharmacologists, and clinical researchers dedicated to making peptide science accessible. Every article is reviewed for accuracy against peer-reviewed sources and updated as new evidence emerges. ## Citations 1. \[1\] Nicholls SJ, et al. — Muvalaplin, an Oral Small-Molecule Inhibitor of Lipoprotein(a) Formation (KRAKEN Phase 2), JAMA / ACC (2024) [Source](https://www.acc.org/latest-in-cardiology/clinical-trials/2024/11/17/17/01/kraken) 2. \[2\] Nicholls SJ, et al. — Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial (Phase 1), JAMA (2023) [Source](https://pubmed.ncbi.nlm.nih.gov/37638695/) 3. \[3\] KRAKEN — LY3473329 (Muvalaplin) in Adults With Elevated Lp(a) (ClinicalTrials.gov NCT05563246) [Source](https://clinicaltrials.gov/study/NCT05563246) 4. \[4\] MOVE-Lp(a) — Muvalaplin Cardiovascular Outcomes Trial (ClinicalTrials.gov NCT07157774) [Source](https://clinicaltrials.gov/study/NCT07157774) 5. \[5\] Lilly's muvalaplin lowered lipoprotein(a) by up to 85% at the highest tested dose — Eli Lilly (2024) [Source](https://investor.lilly.com/news-releases/news-release-details/lillys-muvalaplin-lowered-lipoproteina-levels-adults-high-risk) **Disclaimer:** This article is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider. [Read full research disclaimer →](/research-disclaimer) ## Related Articles [![Research & Compounds cover image](/assets/blog-peptide-guides-BQE1jAYz.jpg)](/blog/olpasiran-amgen-oceana-outcomes-sirna-lp-a-lipoprotein-a-apolipoprotein-a-galnac-mrna-silencing-cardiovascular-outcomes-august-6-2026) Research & Compounds [ ### Olpasiran: The Quarterly Injection That Silences Lp(a) at the Gene — Inside Amgen's OCEAN(a)-Outcomes Readout (August 6, 2026) ](/blog/olpasiran-amgen-oceana-outcomes-sirna-lp-a-lipoprotein-a-apolipoprotein-a-galnac-mrna-silencing-cardiovascular-outcomes-august-6-2026) About one in five people inherit high lipoprotein(a) — a genetic driver of heart attacks and strokes that diet, statins, and PCSK9 inhibitors can't touch. Olpasiran, an siRNA from Amgen, silences the gene behind it and cuts Lp(a) by up to ~97% with a shot every 12 weeks. 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