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● TRACKER Updated 5d ago · 47 sources tracked

The Heart Drug Pelacarsen Fails, Shocking Novartis and Cardiologists

A major Novartis shareholder demands a board shake-up to improve corporate governance following a record drop in share prices. The decline follows consecutive trial failures, including the phase 3 Lp(a)HORIZON trial for the heart drug pelacarsen, which missed its primary endpoint. Although the antisense oligonucleotide successfully lowered lipoprotein(a) levels, it failed to decrease major cardiovascular events in patients with established cardiovascular disease. Consequently, Novartis stopped another phase 3 cardiovascular study of pelacarsen, known as Lp(a)FRONTIERS PEARL, in patients with acute coronary syndrome.

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  • ✓ The phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary composite cardiovascular endpoint.
  • ✓ Novartis reported on September 4, 2026, that the pelacarsen trial failed to produce a statistically significant decrease in major cardiovascular events.
  • ✓ A major shareholder in Novartis called for a board shake-up to improve corporate governance after shares suffered a record fall following back-to-back trial setbacks.
  • ✓ Novartis Pharmaceuticals has stopped Lp(a)FRONTIERS PEARL, a phase 3 cardiovascular study of pelacarsen in patients with acute coronary syndrome.
🛡️ Source Corroboration: 47 independent reporting domains (100% confidence) ⏱ Read time: ~2 min

What changed

A major Novartis shareholder is now demanding a board shake-up, and the company has halted an additional phase 3 study of pelacarsen for acute coronary syndrome.

Live updates

  1. Novartis Faces Shareholder Pressure After Pelacarsen Trial Fails

    A major Novartis shareholder demands a board shake-up to improve corporate governance following a record drop in share prices. The decline follows consecutive trial failures, including the phase 3 Lp(a)HORIZON trial for the heart drug pelacarsen, which missed its primary endpoint. Although the antisense oligonucleotide successfully lowered lipoprotein(a) levels, it failed to decrease major cardiovascular events in patients with established cardiovascular disease. Consequently, Novartis stopped another phase 3 cardiovascular study of pelacarsen, known as Lp(a)FRONTIERS PEARL, in patients with acute coronary syndrome.

    Why it matters

    The unexpected failure of pelacarsen challenges established assumptions regarding biomarker-outcome relationships in cardiovascular drug development. Alongside disappointments from other recent trials, the setback forces a reexamination of how lowering specific blood markers translates into actual clinical outcomes for patients. Discontent among investors has intensified following these clinical roadblocks.

    What is confirmed

    • The phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary composite cardiovascular endpoint.
    • Novartis reported on September 4, 2026, that the pelacarsen trial failed to produce a statistically significant decrease in major cardiovascular events.
    • A major shareholder in Novartis called for a board shake-up to improve corporate governance after shares suffered a record fall following back-to-back trial setbacks.
    • Novartis Pharmaceuticals has stopped Lp(a)FRONTIERS PEARL, a phase 3 cardiovascular study of pelacarsen in patients with acute coronary syndrome.

    What to watch next

    • Whether the Novartis board undergoes structural changes following shareholder pressure
    • Further scientific data releases or analyses explaining the failure of the lipoprotein(a) hypothesis in clinical trials
    Sources used for this update (6)
    1. live.euronext.com — Exclusive-Major Novartis shareholder calls for board shake-up ...
    2. www.youtube.com — The Drug Lowered Lp(a). So Why Didn't the Trial Prove a Heart ...
    3. www.pharmacytimes.com — Pelacarsen, Ziltivekimab Miss CV End Points: What to Know
    4. trial.medpath.com — Pelacarsen and Ziltivekimab Miss Cardiovascular End Points in ...
    5. www.trialticker.com — Novartis Pharmaceuticals stops Phase 3 ACS study Lp (a ...
    6. finance.yahoo.com — Novartis Discontinues Mid-Stage Lupus Trial In Latest ...
    confidence 100%

  2. Pelacarsen Phase 3 Trial Failure Shocks Cardiologists

    Novartis faces intense scrutiny after the Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint. Although the drug sharply reduced lipoprotein(a) levels, it failed to produce a statistically significant decrease in major cardiovascular events among patients with established cardiovascular disease. Experts state that it is too early to discard the lipoprotein(a) hypothesis despite the trial missing its primary goal. The unexpected failure raises questions about biomarker-outcome relationships in cardiovascular drug development, joining recent setbacks for other highly anticipated cardiovascular outcome trials.

    Why it matters

    The unexpected failure of pelacarsen follows the setback of the IL-6 antibody ziltivekimab in the ZEUS trial. Both medications hit their biological targets in the blood yet failed to prove a clinical benefit in major outcome trials. These consecutive failures of highly anticipated cardiovascular drugs have left cardiologists questioning established biomarker-outcome relationships.

    What is confirmed

    • The Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint.
    • Pelacarsen sharply reduced lipoprotein(a) levels but failed to produce a statistically significant decrease in major cardiovascular events.
    • Experts state that it is not yet time to give up on the lipoprotein(a) hypothesis.

    What to watch next

    • Further analysis of the Lp(a)HORIZON trial data by Novartis and independent researchers
    • Decisions by cardiologists and drug developers regarding future research on the lipoprotein(a) hypothesis
    Sources used for this update (5)
    1. pharmaphorum.com — Tenax trounced by phase 3 heart failure readout | pharmaphorum
    2. www.medscape.com — Experts Say It’s Too Early to Ditch the Lp(a) Hypothesis - Today on Medscape
    3. www.clinicaltrialvanguard.com — Pelacarsen Fails to Meet Primary Endpoint in Phase 3 Lp(a) Trial
    4. www.menshb.com — The Most Promising New Drug for Lowering a Dangerous Type of ...
    5. hillarylinmd.com — The Drug Lowered Lp(a). So Why Didn't the Trial Prove a Heart ...
    confidence 100%

  3. Novartis Drug Fails to Reduce Cardiovascular Events

    Novartis faces intense scrutiny after the Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint. Although the drug sharply reduced lipoprotein(a) levels, it failed to produce a statistically significant decrease in major cardiovascular events among patients with established cardiovascular disease. This unexpected trial failure joins the setback of the IL-6 antibody ziltivekimab in the ZEUS trial, as two of the most anticipated cardiovascular outcome trials of the decade have failed despite hitting their biological targets in the blood.

    Why it matters

    The heart is the main organ of the cardiovascular system and pumps blood through blood vessels. The circulatory system carries oxygen and nutrients to tissues while removing metabolic waste like carbon dioxide. Clinical trials test whether targeted biological reductions translate into measurable improvements in patient outcomes.

    What is confirmed

    • The heart is a muscular organ that pumps blood through blood vessels to form the circulatory system.
    • The heart is divided into four chambers consisting of upper atria and lower ventricles.

    What to watch next

    • Further announcements from Novartis regarding the future of the pelacarsen clinical program
    • Additional data releases concerning the ZEUS trial and ziltivekimab
    Sources used for this update (6)
    1. en.wikipedia.org — Heart - Wikipedia
    2. en.wikipedia.org — Heart (band) - Wikipedia
    3. my.clevelandclinic.org — Heart: Anatomy & Function - Cleveland Clinic
    4. www.webmd.com — Heart Anatomy, Function, and Blood Circulation - WebMD
    5. simple.wikipedia.org — Heart - Simple English Wikipedia, the free encyclopedia
    6. www.medicalnewstoday.com — The heart: Anatomy, how it works, and more - Medical News Today
    confidence 50%

  4. Pelacarsen Trial Failure Challenges Lipoprotein(a) Strategy

    Novartis faces intense scrutiny after the Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint. Although the drug sharply reduced lipoprotein(a) levels, it failed to produce a statistically significant decrease in major cardiovascular events among patients with established cardiovascular disease. This unexpected trial failure joins the setback of the IL-6 antibody ziltivekimab in the ZEUS trial, as two of the most anticipated cardiovascular outcome trials of the decade have failed despite hitting their biological targets in the blood.

    Why it matters

    Both pelacarsen and ziltivekimab successfully altered blood biomarkers without reducing major cardiovascular events. Experts attribute these failures to patient selection methods that relied on blood concentrations rather than proving the targeted pathway actively drove disease in the arterial wall. These results challenge drug classes built on strong genetic signals and raise difficult questions about how well DNA evidence predicts heart disease treatment outcomes.

    What is confirmed

    • The Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint and failed to produce a statistically significant decrease in major cardiovascular events.
    • Pelacarsen sharply reduced lipoprotein(a) levels but did not reduce major cardiovascular events among patients with established cardiovascular disease.
    • No drug is currently approved to lower lipoprotein(a) levels.
    • The IL-6 antibody ziltivekimab and the lipoprotein(a)-lowering antisense drug pelacarsen both hit their targets in the blood, yet neither reduced major cardiovascular events.
    • Amgen reported encouraging mid-stage results for its olpasiran candidate and plans to move ahead swiftly with a Phase 3 programme.

    Still unconfirmed

    • Both trials selected patients by a blood concentration rather than by evidence that the targeted pathway was driving disease in the arterial wall.

    What to watch next

    • Progression of Amgen's olpasiran Phase 3 programme
    • Further analysis regarding patient selection criteria in cardiovascular outcome trials
    Sources used for this update (2)
    1. pharmaphorum.com — Chasing Novartis, Amgen ushers Lp (a) drug into phase 3
    2. ecgwaves.com — ZEUS and Lp(a)HORIZON: why ziltivekimab and pelacarsen failed
    confidence 100%

  5. Heart Drug Pelacarsen Fails Phase 3 Trial

    Novartis faces a major hurdle after its Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint. Although the drug sharply reduced lipoprotein(a) levels, it failed to produce a statistically significant decrease in major cardiovascular events among patients with established cardiovascular disease. This unexpected trial failure casts doubt on a drug class built on strong genetic signals and raises difficult questions about how well DNA evidence predicts heart disease treatment outcomes. No drug is currently approved to lower lipoprotein(a) levels.

    Why it matters

    The unexpected setback challenges the foundational hypothesis that lowering lipoprotein(a) directly translates to clinical cardiovascular benefits. Researchers and cardiologists now question how to translate genetic associations into successful therapies when clinical endpoints are missed.

    What is confirmed

    • The Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint.
    • Pelacarsen sharply lowered lipoprotein(a) levels.
    • The drug failed to produce a statistically significant reduction in major cardiovascular events among patients with established cardiovascular disease.
    • No drug is currently approved to lower lipoprotein(a).

    Still unconfirmed

    • The broader scientific community is re-evaluating the validity of targeting lipoprotein(a) based on genetic data alone following the trial results.

    What to watch next

    • Further peer-reviewed analyses on the Lp(a) hypothesis
    • Subgroup data releases from the Lp(a)HORIZON trial
    • Strategic updates from Novartis regarding its cardiovascular drug pipeline
    Sources used for this update (2)
    1. www.healthline.com — FDA Issues Class II Blood Pressure Medication Recall, Over 13,000 Bottles Affected
    2. thecodon.substack.com — Taking bets on the Lp (a) hypothesis - by Marios Georgakis
    confidence 100%

  6. Novartis Pelacarsen Trial Fails to Reduce Heart Events

    Novartis suffered a major setback when its Phase 3 Lp(a)HORIZON trial for pelacarsen missed its primary endpoint. Although the drug sharply lowered lipoprotein(a) levels, it failed to produce a statistically significant reduction in major cardiovascular events among patients with established cardiovascular disease. The unexpected trial failure bruised the case for a drug class built on strong genetic signals and raised hard questions about what DNA evidence can actually predict for heart disease treatments. No drug is currently approved to lower lipoprotein(a).

    Why it matters

    Pelacarsen is an antisense-based drug designed to target lipoprotein(a). The setback carries implications beyond Novartis, potentially reshaping the competitive landscape for Lp(a) reduction therapies and benefiting competing programs from CRISPR and Ionis. And Novo Nordisk's ziltivekimab similarly nailed its biomarker targets yet failed to reduce cardiovascular events in large heart disease trials.

    What is confirmed

    • Novartis experienced a setback in its Phase 3 Lp(a)HORIZON study after pelacarsen failed to significantly reduce major cardiovascular events.
    • Pelacarsen sharply lowered lipoprotein(a) levels but missed its cardiovascular trial goal.
    • The failure of pelacarsen could reshape the competitive landscape for Lp(a) reduction therapies, potentially benefiting CRISPR and Ionis programs.

    Still unconfirmed

    • Physicians are advocating for diet-based cardiovascular prevention strategies following the trial miss.

    What to watch next

    • Developments in competing Lp(a) reduction programs from CRISPR and Ionis.
    • Further clinical trial updates and regulatory decisions regarding lipoprotein(a) medications.
    Sources used for this update (10)
    1. finance.yahoo.com — Failure of Novartis’ Pelacarsen Could Reshape the Lp(a) Race for CRISPR and Ionis
    2. nexi.fund — Pelacarsen Deeply Lowered Lp (a). Cardiovascular Events ...
    3. catalystalert.io — Failure of Novartis’ Pelacarsen Could Reshape the Lp(a) Race ...
    4. www.el-fondo.com — Novartis Faces Phase 3 Setback in Pelacarsen Trial
    5. imedic.health — Pelacarsen Heart Trial: What Does the Lp (a) Setback | iMedic
    6. pauldthompsonmd.substack.com — Reducing Lipoprotein a Failed to Reduce Atherosclerotic Events
    7. biotechmorning.com — Genetics Said These Heart Drugs Should Work. The Patients ...
    8. usinsider.com — Kumara Sidhartha on Lp (a) Drug Trial and Diet - usinsider.com
    9. veevohealth.com — Lp(a) Medications and Clinical Trial Updates - Veevo Health
    10. pharmaphorum.com — Dosing prompts Novartis to tap Ionis for second Lp(a) drug
    confidence 100%

  7. Novartis Pelacarsen Trial Failure Triggers Biotech Sector Sell-off

    Novartis announced that pelacarsen failed its Phase 3 Lp(a)HORIZON trial after it failed to reduce major cardiovascular events in patients with established cardiovascular disease. While the drug successfully lowered lipoprotein(a) levels, it did not prevent heart attacks, strokes, or cardiovascular deaths. The failure shocked cardiologists who expected the drug to be a primary tool against heart attacks. The result caused a broader biotech market decline, including a 6.2% weekly slide for BioNTech as investor sentiment soured across the sector.

    Why it matters

    The trial results create a biomarker paradox because clinical benefits did not follow a significant reduction in genetic cholesterol markers. This outcome raises questions about the efficacy of targeting Lp(a) once heart disease is already present.

    What is confirmed

    • The Phase 3 Lp(a)HORIZON trial found pelacarsen did not reduce major cardiovascular events in patients with established cardiovascular disease.
    • Pelacarsen successfully lowered Lp(a) levels during the clinical trial.

    What to watch next

    • Analysis of why biomarker reduction failed to translate into clinical outcomes
    • Novartis official statement on the future of the pelacarsen program
    Sources used for this update (3)
    1. medicalxpress.com — Cardiologists expected this new drug to prevent heart attacks—so why did it fail?
    2. www.thecardiologyadvisor.com — Pelacarsen Misses CV Risk Endpoint in Lp(a)HORIZON Trial
    3. www.ad-hoc-news.de — BioNTech's Rough Week: A Sector Shock, a Founder's Sell-Down, and a Pipeline That Says Otherwise
    confidence 100%

  8. Novartis Pelacarsen Phase 3 Failure Challenges Genetic Cholesterol Theories

    Novartis experimental drug pelacarsen failed its Phase 3 Lp(a)HORIZON trial after failing to reduce strokes, heart attacks, or cardiovascular deaths. The drug successfully lowered the genetic cholesterol marker lipoprotein(a) by 80% in over 8,000 patients, but these biomarker reductions did not translate into clinical benefits. The results caused Novartis shares to drop 1.9%, erasing CHF4.9 billion in value, and triggered share price declines for Royalty Pharma, Amgen, and other rivals. Experts describe the result as a biomarker paradox that questions the efficacy of targeting Lp(a) after heart disease has already developed.

    Why it matters

    Lipoprotein(a) is a genetic risk factor for heart disease. This trial failure suggests that slashing this specific marker may not prevent cardiac events in vulnerable groups, such as South Asians. The outcome puts the entire class of Lp(a) drugs under scrutiny.

    What is confirmed

    • Pelacarsen failed to reduce the risk of heart attacks, strokes, or cardiovascular death.
    • The drug lowered Lp(a) levels in more than 8,000 patients.
    • Novartis shares fell 1.9%, resulting in a loss of CHF4.9 billion.
    • The drug reduced Lp(a) cholesterol by 80%.

    Still unconfirmed

    • Novartis suffered three clinical failures in one week that vaporized more than $40 billion in market value.
    • Targeting Lp(a) after disease onset may be ineffective for South Asian populations.
    • Royalty Pharma shares fell nearly 6% in Tuesday trading.

    What to watch next

    • Clinical trial results from Amgen or Eli Lilly regarding Lp(a) targeting therapies.
    • Novartis official statement on the biomarker paradox and future cardiovascular strategy.
    Sources used for this update (7)
    1. finance.yahoo.com — Novartis pelacarsen Lp(a) trial fails, raising doubts for Amgen, Lilly
    2. english.gujaratsamachar.com — Novartis Heart Drug Fails Phase 3 Trial: Cutting Genetic Cholesterol Marker Fails to Stop Cardiac Attacks
    3. allsci.com — Novartis’s pelacarsen misses Phase III endpoint despite deep Lp(a) lowering
    4. finance.yahoo.com — Royalty Pharma Shares Fall After Novartis' Pelacarsen Fails Trial
    5. www.capitalbrief.com — Oil close to USD100 amid US strikes near Kharg Island
    6. www.yahoo.com — Doctors stunned after promising heart drug fails major study
    7. finance.biggo.com — Stephen Anson: Novartis's Pelacarsen Failure Puts the Entire Lp(a) Drug Field on Trial
    confidence 90%

  9. Pelacarsen Fails Late-Stage Trial, Jolting Novartis and Market

    Novartis shares fell 1.9 percent, erasing CHF4.9 billion after its experimental heart drug pelacarsen failed a late-stage trial. Although the therapy successfully lowered the targeted biomarker lipoprotein(a), it did not reduce deaths, heart attacks, or strokes. The failure missed the primary endpoint of the Lp(a)HORIZON study, shocking cardiologists and dealing a blow to expectations for this new cardiovascular treatment approach. Shares of related companies, including Amgen, also dropped following the disappointing results from the trial.

    Why it matters

    The failed late-stage trial evaluated the investigational cardiovascular therapy pelacarsen to see if lowering lipoprotein levels could prevent major adverse cardiovascular events in more than 8,000 patients. Instead of demonstrating a reduction in heart attacks and strokes, the trial forced investors to look toward upcoming pipeline tests. This setback disrupts previous confidence in targeting lipoprotein(a) as a viable strategy to manage heart disease.

    What is confirmed

    • Novartis shares fell 1.9 percent, erasing CHF4.9 billion following the drug trial failure.
    • Pelacarsen successfully lowered lipoprotein(a) but did not cut deaths, heart attacks, or strokes.
    • The late-stage trial failure missed its primary endpoint.
    • Amgen shares dropped following the disappointing trial results.

    What to watch next

    • Further market reactions and financial disclosures from Novartis and related companies like Amgen.
    • Decisions by Novartis regarding future investments in its drug pipeline following the trial failure.
    Sources used for this update (4)
    1. finance.yahoo.com — Novartis Late-Stage Cardiovascular Outcome Study Fails, Stock Down
    2. www.briefs.co — Novartis Heart Drug Misses Final Test, Jolting Hopes for a New Heart-Disease Approach
    3. finance.yahoo.com — Novartis Falls 1.9% as Pelacarsen Failure Erases CHF4.9 Billion
    4. finance.biggo.com — Novartis Heart Drug Pelacarsen Fails Late-Stage Trial, Sending Shares Down
    confidence 100%

  10. Novartis Heart Drug Pelacarsen Fails Late-Stage Trial

    Novartis and Ionis announced that their experimental cardiovascular drug pelacarsen failed to meet its primary endpoint in a late-stage clinical trial. The Phase III Lp(a)HORIZON study evaluated more than 8,000 patients with elevated lipoprotein levels to determine if the treatment could reduce the risk of major adverse cardiovascular events compared to a placebo. Instead of showing a reduction in heart attacks and strokes, the therapy missed its primary goal, shocking cardiologists and triggering stock selloffs for Novartis and related companies.

    Why it matters

    Pelacarsen was designed as a novel approach to lower genetically driven cardiovascular risk factors by targeting lipoprotein. The failure of the first Phase 3 outcomes trial for an Lp(a)-lowering drug raises significant concerns regarding the viability of similar therapies across the industry. Shares of Novartis fell more than three percent in Zurich following the announcement.

    What is confirmed

    • Novartis and Ionis announced that pelacarsen failed its late-stage Phase III trial.
    • The Lp(a)HORIZON trial enrolled more than 8,000 patients with elevated lipoprotein levels.
    • Pelacarsen did not meet its primary endpoint to reduce the risk of cardiovascular events compared with a placebo.
    • Novartis shares fell more than 3 percent following the trial failure.

    What to watch next

    • Broader industry implications and pipeline updates for other Lp(a)-targeting therapies from rival developers.
    • Further market reaction and stock performance for Novartis, Ionis, and Amgen.
    Sources used for this update (13)
    1. The New York Times — Another Heart Drug Fails, Shocking Cardiologists
    2. reuters.com — Ionis, Novartis' key experimental heart drug fails in late-stage trial
    3. Bloomberg.com — Novartis Drug Fails Key Test for New Heart Disease Approach
    4. WSJ — Novartis Says Closely Watched Cholesterol Study Failed to Meet Goal
    5. Yahoo Finance — NVS, IONS, AMGN Stocks Drop After-Hours — What’s Driving The Selloff?
    6. fiercebiotech.com — Novartis Lp(a) drug fails to lower cardiovascular risk in closely watched ph. 3 trial
    7. en.ilsole24ore.com — Novartis shares fall in Zurich as cardiovascular drug fails final trial
    8. www.yahoo.com — Novartis’ pelacarsen fails to meet primary endpoint in Lp(a)HORIZON trial
    9. finance.yahoo.com — Novartis Shares Fall After Pelacarsen Misses Primary Goal in Late-Stage Heart Trial
    10. www.marketscreener.com — Novartis pelacarsen fails Phase III trial
    11. www.globalbankingandfinance.com — Novartis shares down as failed cholesterol drug study increases pipeline pressure
    12. blockonomi.com — Novartis (NVS) Stock Drops 3% as Pelacarsen Heart Drug Disappoints in Key Trial
    confidence 100%
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