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    PCSK9 inhibitors

    Also known as PCSK9 inhibitor, evolocumab, Repatha, alirocumab, Praluent, inclisiran, Leqvio, enlicitide, Lipfendra

    PCSK9 inhibitors are cholesterol drugs that target the PCSK9 protein. Evolocumab cut LDL by 59% in its main outcome trial, and both it and alirocumab reduced cardiovascular events in large trials.[1][2] Newer forms include inclisiran, an injection given twice a year, and enlicitide (Lipfendra), which in July 2026 became the first FDA-approved oral PCSK9 inhibitor. Outcome trials for both are still running.[3][4][5][6]

    Editor reviewedStrict sourcingUpdated WikiHealth and medicine, GLP-1 and metabolic medicine, Life sciences
    Key facts

    PCSK9 inhibitors are a family of cholesterol-lowering drugs that act on the PCSK9 protein. They are usually added when statins alone do not lower LDL enough, and the 2026 US guideline lists PCSK9 antibodies among its evidence-based add-on options.[7] In 2026 the class gained its first pill.[4]

    This page is general information, not medical advice. Talk to a clinician about whether any of these drugs is right for you.

    The antibodies: evolocumab and alirocumab

    In FOURIER, 27,564 people with atherosclerotic disease on statins were given evolocumab injections or placebo. Evolocumab lowered LDL by 59% to a median of 30 mg/dL and reduced the primary cardiovascular endpoint (HR 0.85). Injection-site reactions were slightly more common (2.1% vs 1.6%).[1] In ODYSSEY OUTCOMES, alirocumab reduced recurrent ischaemic events after acute coronary syndrome, 9.5% versus 11.1% (HR 0.85).[2]

    In November 2025, VESALIUS-CV extended the evidence to prevention of a first event. Among 12,257 people with atherosclerosis or diabetes but no previous heart attack or stroke, evolocumab lowered the 5-year risk of a first major event from 8.0% to 6.2% (HR 0.75).[8] The 2026 guideline’s authors wrote that VESALIUS-CV should lead future updates toward a single LDL goal below 55 mg/dL for everyone with atherosclerotic disease.[9]

    Inclisiran

    Inclisiran (Leqvio) blocks the liver’s production of PCSK9 instead of binding the protein. In ORION-10 and ORION-11, injections on day 1, day 90 and every six months lowered LDL by about 50%.[3] The FDA approved it in December 2021.[10] The 2026 US guideline notes that it is still being studied to show whether it reduces cardiac events.[7] Two outcome trials with more than 33,000 participants combined, ORION-4 and VICTORION-2P, were active as of October 2026.[5]

    Enlicitide (Lipfendra), the oral PCSK9 inhibitor

    Enlicitide is a macrocyclic peptide taken as a 20 mg tablet once a day.[4] In CORALreef Lipids (2,909 adults), it lowered LDL by 55.8 percentage points more than placebo at 24 weeks. It also lowered apoB and Lp(a), and adverse events did not appear to differ from placebo.[11] The FDA approved it in July 2026 for adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.[4] In the HeFH trial, diarrhoea (7% vs 2%) and dizziness (9% vs 4%) were more common than with placebo.[12] Merck says it is not yet known whether the drug reduces cardiovascular events. Its CORALreef Outcomes trial has enrolled over 14,500 people and is expected to reach primary completion in 2029.[6]

    Permanent editing

    Gene editing aims to switch off the PCSK9 gene permanently. Eli Lilly agreed to buy Verve Therapeutics in 2025 for its PCSK9 base editor, VERVE-102; see base-editing and eli-lilly.[13] For a comparison with statins and other drugs, see statins and the cholesterol drugs guide.

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    Obicetrapib is an oral CETP inhibitor that lowers LDL cholesterol. EU-approved in September 2026 as Ubeslo and Evlarco; PREVAIL outcome data are pending.

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    Questions readers ask

    What are PCSK9 inhibitors?

    Cholesterol drugs that target the PCSK9 protein. They include the antibodies evolocumab and alirocumab, inclisiran, which blocks the liver's production of PCSK9, and the oral drug enlicitide.[1][3][4]

    Do PCSK9 inhibitors prevent heart attacks?

    The antibodies do. Evolocumab reduced cardiovascular events in FOURIER and first events in VESALIUS-CV, and alirocumab reduced recurrent events in ODYSSEY OUTCOMES. Outcome results for inclisiran and enlicitide are not yet available.[1][8][2][5][6]

    Is there a PCSK9 pill?

    Yes. Merck's enlicitide (Lipfendra) was approved by the FDA in July 2026 as a once-daily 20 mg tablet. It lowered LDL by about 56% versus placebo at 24 weeks in its main trial.[4][12]

    What are the side effects of PCSK9 inhibitors?

    In FOURIER, injection-site reactions were slightly more common with evolocumab than placebo (2.1% vs 1.6%). In the enlicitide HeFH trial, diarrhoea and dizziness were more common than with placebo.[1][12]

    Sources

    · 14 claims from 7 publishers

    Each numbered claim is a statement we checked against the sources listed with it. Tap a number in the text to see its sources in place.

    1. [1]

      In FOURIER (27,564 patients with atherosclerotic cardiovascular disease on statins, median follow-up 2.2 years), the PCSK9 antibody evolocumab cut LDL cholesterol by 59% versus placebo to a median of 30 mg/dL and reduced the primary cardiovascular endpoint (hazard ratio 0.85); injection-site reactions were more common (2.1% vs 1.6%). confirmedas of 2026-10-11

    2. [2]

      In ODYSSEY OUTCOMES (18,924 patients 1 to 12 months after an acute coronary syndrome on high-intensity statins, median follow-up 2.8 years), the PCSK9 antibody alirocumab reduced recurrent ischaemic cardiovascular events (9.5% vs 11.1%; hazard ratio 0.85). confirmedas of 2026-10-11

    3. [3]

      Inclisiran blocks the liver's production of PCSK9; in the ORION-10 and ORION-11 trials (1,561 and 1,617 patients on maximum tolerated statins), injections on day 1, day 90 and every 6 months cut LDL cholesterol by about 50% versus placebo, with more injection-site reactions. confirmedas of 2026-10-11

    4. [4]

      The FDA approved Merck's enlicitide (Lipfendra) 20 mg tablets in July 2026 (FDA action date 15 July; Merck announced it on 16 July) to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, making it the first FDA-approved oral PCSK9 inhibitor. confirmedas of 2026-10-11

    5. [5]

      Two large inclisiran outcome trials were active but not recruiting as of October 2026, ORION-4 (16,124 participants, estimated primary completion October 2026) and VICTORION-2P (17,004 participants, estimated primary completion May 2027). confirmedas of 2026-10-11

    6. [6]

      Merck states it is not yet known whether Lipfendra reduces cardiovascular illness and death; its CORALreef Outcomes trial has enrolled over 14,500 participants, with estimated primary completion in November 2029. confirmedas of 2026-10-11

    7. [7]

      If lifestyle and statins do not lower LDL cholesterol enough, the 2026 guideline recommends adding nonstatin therapy such as ezetimibe, bempedoic acid or a PCSK9 monoclonal antibody, and notes that inclisiran is still being studied to show whether its LDL lowering reduces cardiac events. confirmedas of 2026-10-11

    8. [8]

      In VESALIUS-CV (12,257 patients with atherosclerosis or diabetes but no previous heart attack or stroke, median follow-up 4.6 years), evolocumab lowered the risk of a first major cardiovascular event versus placebo (5-year estimate 6.2% vs 8.0%; hazard ratio 0.75), with no evidence of a difference in safety events; results were published in November 2025. confirmedas of 2026-10-11

    9. [9]

      In an editorial comment, the guideline's chair and vice-chair wrote that VESALIUS-CV results should lead future updates to adopt a single care pathway for all patients with ASCVD with an LDL goal below 55 mg/dL. confirmedas of 2026-10-11

    10. [10]

      The FDA approved Novartis's inclisiran (Leqvio, NDA 214012) as a new molecular entity on 22 December 2021. confirmedas of 2026-10-11

    11. [11]

      In the CORALreef Lipids trial (2,909 adults with or at risk of atherosclerotic cardiovascular disease), oral enlicitide 20 mg daily lowered LDL cholesterol by 55.8 percentage points more than placebo at week 24, also lowered non-HDL cholesterol, apolipoprotein B and Lp(a), and adverse events did not appear to differ from placebo. confirmedas of 2026-10-11

    12. [12]

      Merck reported that Lipfendra reduced LDL cholesterol by 56% versus placebo at week 24 in CORALreef Lipids and by 59% in CORALreef HeFH; in CORALreef HeFH, diarrhoea (7% vs 2%) and dizziness (9% vs 4%) were more common than with placebo. confirmedas of 2026-10-11

    13. [13]

      On 17 June 2025 Eli Lilly agreed to acquire Verve Therapeutics for $10.50 per share in cash plus a contingent value right of up to $3.00 per share; Verve's lead program VERVE-102 is designed to permanently turn off the PCSK9 gene in the liver to lower cholesterol. confirmedas of 2026-10-10

    14. [14]

      In BROADWAY (2,530 patients with ASCVD or heterozygous familial hypercholesterolemia on maximum tolerated lipid-lowering therapy), obicetrapib 10 mg daily, a selective CETP inhibitor, lowered LDL cholesterol by 32.6 percentage points more than placebo at day 84, with similar adverse-event rates. confirmedas of 2026-10-11

    Revision history (1)
    1. Page created.

    Created Oct 11, 2026. Last reviewed by an editor on Oct 11, 2026. Next scheduled review: Jan 11, 2027.

    Cite this page

    "PCSK9 inhibitors." ContentLora, updated Oct 11, 2026. https://contentlora.com/wiki/pcsk9-inhibitors

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