Preval HealthTherapies
Cholesterol drugs and how they work
Tap a drug on the map to see where it works in the body. 14 of the 22 groups below are approved today (including low-cost generics). The other 8 are still in trials.
Mechanism text curated October 25, 2026. Trial and approval status refreshes monthly from ClinicalTrials.gov, PubMed and openFDA (last run October 27, 2026).
Map of where each medicine acts
Approved today
Lowering LDL cholesterol
- Approved (generic)PillStatinsActs on HMG-CoA reductase · liverLDL-C −30% to ≥50% by intensity; major vascular events ↓ ≈ 22% per mmol/L LDL-C
- Approved 2020PillBempedoic acid (Nexletol, Nexlizet)Acts on ATP-citrate lyase (upstream of HMGCR) · liverLDL-C −18 pp on a statin, −21 pp without; MACE HR 0.87 (CLEAR Outcomes)
- Approved (generic)PillEzetimibe (Zetia)Acts on NPC1L1 · intestineLDL-C ≈ −18% alone, ≈ −25% added to a statin; MACE ↓ (IMPROVE-IT)
- Approved (generic)PillBile acid sequestrants (colesevelam)Acts on Bile acids · gut lumenLDL-C ≈ −15% to −20% (colesevelam −16.7 pp vs placebo)
- Approved 2015Injected proteinEvolocumab (Repatha) and alirocumab (Praluent)Acts on PCSK9 protein · bloodLDL-C ≈ −60%; Lp(a) −20% to −30%; MACE HR 0.85 (FOURIER, ODYSSEY)
- Approved Dec 2025; no outcome trialInjected proteinLerodalcibep (Lerochol)Acts on PCSK9 protein · bloodLDL-C −56% vs placebo at 52 weeks (LIBerate-HR)
- Approved Jul 2026; outcome trial ongoingPillEnlicitide (Lipfendra)Acts on PCSK9 proteinLDL-C −55.8 pp at 24 weeks (CORALreef Lipids)
- Approved 2021; outcome trials ongoingsiRNA injectionInclisiran (Leqvio)Acts on PCSK9 mRNA · liverLDL-C ≈ −50% (ORION-10/11)
- Approved 2012 (HoFH only)PillLomitapide (Juxtapid)Acts on MTP · liver and intestineLDL-C ≈ −50% in HoFH (−53.5% in children)
Lowering triglycerides
- Approved 2021 (HoFH)Injected proteinEvinacumab (Evkeeza)Acts on ANGPTL3 protein · bloodLDL-C −49 pp in HoFH (ELIPSE); TG ↓
- Olezarsen approved 2024; volanesorsen EU onlyAntisense injectionOlezarsen (Tryngolza) and volanesorsenActs on APOC3 mRNA · liverOlezarsen TG −49 to −58 pp (moderate HTG); volanesorsen TG −77% (FCS)
- Approved Nov 2025 (FCS)siRNA injectionPlozasiran (Redemplo)Acts on APOC3 mRNA · liverTG −80% (median, FCS; PALISADE)
- Approved (generic)PillFibrates (fenofibrate)Acts on PPARα · liver nucleusLower TG; no reduction in the primary coronary outcome in FIELD
- ApprovedPillIcosapent ethyl (Vascepa)Acts on Multiple (liver TG synthesis, membranes)MACE HR 0.75 (REDUCE-IT)
In trials, not yet approved
Lowering LDL cholesterol
- Phase 3 (AZURE-Outcomes)PillAZD0780 (laroprovstat)Acts on PCSK9 proteinLDL-C −50.7% at 30 mg (phase 2b PURSUIT)
- Phase 2Gene editingVERVE-102Acts on PCSK9 gene · liverPCSK9 −88%, LDL-C −62% at 1.0 mg/kg (phase 1b)
- Phase 3 (PREVAIL outcome trial ongoing)PillObicetrapibActs on CETP · bloodLDL-C −32.6 pp (BROADWAY)
Lowering triglycerides
- Zodasiran phase 3; solbinsiran phase 2siRNA injectionZodasiran and solbinsiranActs on ANGPTL3 mRNA · liverZodasiran: TG −51 to −63 pp, LDL-C −14 to −20 pp (phase 2b). Solbinsiran: apoB −14% at 400 mg (phase 2)
- Phase 1Gene editingCTX310Acts on ANGPTL3 gene · liverANGPTL3 −73% to −80% at 0.7–0.8 mg/kg (phase 1, n = 15)
Lowering lipoprotein(a)
- Phase 3 (outcome trial negative)Antisense injectionPelacarsenActs on LPA mRNA (apo(a)) · liverLp(a) −35% to −80% (phase 2); missed primary endpoint in Lp(a)HORIZON
- Olpasiran, lepodisiran phase 3 outcome trials; zerlasiran phase 2siRNA injectionOlpasiran, lepodisiran and zerlasiranActs on LPA mRNA · liverLp(a) −97% (olpasiran), −94% (lepodisiran), −81% to −86% (zerlasiran), placebo-adjusted
- Phase 3PillMuvalaplinActs on apo(a)–apoB-100 bindingLp(a) −86% (intact assay, 240 mg; KRAKEN)
Five pathways these drugs act on
▸The LDL-receptor cycle
LDL particles are cleared from blood when they bind LDL receptors on liver cells. After the particle is taken in, a receptor normally returns to the surface and can be reused many times. PCSK9 escorts the receptor to the lysosome, where it is destroyed. Every PCSK9-pathway drug (5–10) works by keeping more receptors on the surface.
Drugs on this pathway: Evolocumab (Repatha) and alirocumab (Praluent), Lerodalcibep (Lerochol), Enlicitide (Lipfendra), AZD0780 (laroprovstat), Inclisiran (Leqvio), VERVE-102
▸Cholesterol synthesis and absorption
When the liver has less cholesterol, whether because synthesis is blocked (statins, bempedoic acid) or less arrives from the gut (ezetimibe, bile acid sequestrants), SREBP-2 switches on the LDL-receptor gene and the liver pulls more LDL out of the blood. SREBP-2 also raises PCSK9, which is one reason PCSK9 inhibitors add well to statins.
Drugs on this pathway: Statins, Bempedoic acid (Nexletol, Nexlizet), Ezetimibe (Zetia), Bile acid sequestrants (colesevelam)
▸Triglyceride-rich lipoproteins
VLDL from the liver and chylomicrons from the gut carry triglyceride. Lipoprotein lipase (LPL) on capillary walls breaks it down. ANGPTL3 and apoC-III act as brakes on this process. Removing either brake (11–15) lowers triglycerides, and ANGPTL3 blockade also lowers LDL-C without needing LDL receptors, which matters in homozygous FH.
Drugs on this pathway: Evinacumab (Evkeeza), Zodasiran and solbinsiran, CTX310, Olezarsen (Tryngolza) and volanesorsen, Plozasiran (Redemplo), Lomitapide (Juxtapid), Fibrates (fenofibrate), Icosapent ethyl (Vascepa)
▸Lipoprotein(a)
Lp(a) is an LDL-like particle with an extra protein, apo(a), made from the LPA gene. Its level is about 90% genetically determined. Antisense and siRNA drugs (16, 17) stop apo(a) production; muvalaplin (18) blocks apo(a) from attaching to apoB. Pelacarsen did not meet its primary outcome; other outcome trials are ongoing.
Drugs on this pathway: Pelacarsen, Olpasiran, lepodisiran and zerlasiran, Muvalaplin
▸RNA and gene-editing therapies
These drugs act before a protein is made. siRNA and antisense drugs are attached to GalNAc, which hepatocytes take up, and they destroy one specific mRNA. A dose lasts weeks to months. Gene editors (10, 13) make a permanent single-dose change to the DNA and are in early trials.
Drugs on this pathway: Inclisiran (Leqvio), VERVE-102, Zodasiran and solbinsiran, CTX310, Olezarsen (Tryngolza) and volanesorsen, Plozasiran (Redemplo), Pelacarsen, Olpasiran, lepodisiran and zerlasiran
Pipeline tracker, October 27, 2026
Pulled from ClinicalTrials.gov, PubMed and openFDA. Registries can lag company announcements, so a drug's own page and its sponsor's news come first.
| Agent | Target | Sponsor | Stage | Active trials |
|---|---|---|---|---|
| Enlicitide (Lipfendra) | PCSK9 | Merck | US approved 2026-07-15 | 8 of 34 |
| AZD0780 | PCSK9 | AstraZeneca | Phase 3 | 6 of 21 |
| Lerodalcibep (Lerochol) | PCSK9 | LIB Therapeutics | US approved 2025-12-12 | 5 of 15 |
| Inclisiran (Leqvio) | PCSK9 mRNA | Novartis | US approved 2021-12-22 | 28 of 53 |
| VERVE-102 | PCSK9 gene | Eli Lilly (Verve) | Phase 2 | 2 of 2 |
| CTX310 | ANGPTL3 gene | CRISPR Therapeutics | Phase 1 | 1 of 1 |
| Pelacarsen | LPA mRNA | Novartis / Ionis | Phase 3 | 5 of 13 |
| Olpasiran | LPA mRNA | Amgen | Phase 3 | 3 of 9 |
| Lepodisiran | LPA mRNA | Eli Lilly | Phase 3 | 2 of 7 |
| Zerlasiran | LPA mRNA | Silence Therapeutics | Phase 2 | 0 of 2 |
| Muvalaplin | Lp(a) assembly | Eli Lilly | Phase 3 | 1 of 6 |
| Obicetrapib | CETP | NewAmsterdam / Menarini | Phase 3 | 7 of 29 |
| Olezarsen (Tryngolza) | APOC3 mRNA | Ionis | US approved 2024-12-19 | 4 of 11 |
| Plozasiran (Redemplo) | APOC3 mRNA | Arrowhead | US approved 2025-11-18 | 2 of 11 |
| Zodasiran | ANGPTL3 mRNA | Arrowhead | Phase 3 | 3 of 6 |
| Solbinsiran | ANGPTL3 mRNA | Eli Lilly | Phase 2 | 1 of 3 |
| Evinacumab (Evkeeza) | ANGPTL3 | Regeneron | US approved 2021-02-11 | 1 of 12 |
Latest recorded changes: October 25, 2026, 17 items. See the monthly log.
Common questions
Which new cholesterol drugs have been approved recently?
Registry data as of October 27, 2026 lists these US approvals since 2024: Enlicitide (Lipfendra), 2026-07-15; Lerodalcibep (Lerochol), 2025-12-12; Olezarsen (Tryngolza), 2024-12-19; Plozasiran (Redemplo), 2025-11-18.
Which cholesterol drugs are in phase 3 trials?
As of October 27, 2026: AZD0780, Pelacarsen, Olpasiran, Lepodisiran, Muvalaplin, Obicetrapib, Zodasiran.
Is there a PCSK9 inhibitor in pill form?
Approved Jul 2026; outcome trial ongoing. Enlicitide (Lipfendra) is an oral PCSK9 inhibitor. AZD0780 (laroprovstat) is a second oral PCSK9 inhibitor, Phase 3 (AZURE-Outcomes).
Is any drug approved to lower lipoprotein(a)?
Not yet. As of October 25, 2026, every lipoprotein(a) drug listed here is still in clinical trials (Pelacarsen: Phase 3 (outcome trial negative); Olpasiran, lepodisiran and zerlasiran: Olpasiran, lepodisiran phase 3 outcome trials; zerlasiran phase 2; Muvalaplin: Phase 3), so they are available only through trials.
Educational, not medical advice. Effects are placebo-adjusted results from the main published trial of each agent, not head-to-head comparisons. Investigational agents are available only in clinical trials. Preval Health does not practice medicine; licensed clinicians in a partner network provide care.
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