Ionis: Novartis pelacarsen Phase 3 misses goal
Pelacarsen’s large Phase 3 Lp(a)HORIZON trial in high-risk cardiovascular patients failed its primary endpoint, despite strong Lp(a) lowering and acceptable safety.
Rhea-AI Filing Summary
Ionis Pharmaceuticals, Inc. (IONS) reported that its partner Novartis’ Phase 3 Lp(a)HORIZON cardiovascular outcomes trial of pelacarsen in patients with elevated lipoprotein(a) did not meet its primary endpoint of reducing major cardiovascular events versus placebo. The composite endpoint covered cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization.
Pelacarsen continued to show substantially lower Lp(a) levels and an acceptable safety profile, and full data are planned for presentation at an upcoming medical congress. Ionis discovered and conducted early development of pelacarsen before Novartis licensed global development and commercialization rights in 2019.
Positive
- Pelacarsen achieved substantially lower Lp(a) levels consistent with earlier studies, reinforcing its biological activity against an inherited cardiovascular risk factor.
- The Lp(a)HORIZON trial reported an acceptable safety profile for pelacarsen, supporting its tolerability in a large global cardiovascular outcomes study.
- Ionis continues to emphasize its wholly owned commercial medicines TRYNGOLZA®, DAWNZERA® and ZANVASTRO™ and a broader pipeline beyond pelacarsen.
Negative
- Novartis’ Phase 3 Lp(a)HORIZON trial did not meet its primary endpoint of reducing major cardiovascular events versus placebo, a setback for pelacarsen’s cardiovascular outcomes strategy.
- The negative outcome from a pivotal Phase 3 cardiovascular outcomes trial may limit the near-term therapeutic and commercial potential of pelacarsen in established cardiovascular disease.
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8-K Event Classification
3 items: 7.01, 8.01, 9.01
3 items
Item 7.01
Regulation FD Disclosure
Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 8.01
Other Events
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Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, or exhibit attachments filed with this report.
Key Figures
Trial patients enrolled: 8,323 patients
Elevated Lp(a) prevalence: Approximately 20% of people worldwide
Premature CVD with elevated Lp(a): Nearly one-third
+3 more
6 metrics
Trial patients enrolled
8,323 patients
Phase 3 Lp(a)HORIZON global cardiovascular outcomes trial of pelacarsen
Elevated Lp(a) prevalence
Approximately 20% of people worldwide
Portion of global population with elevated lipoprotein(a) cited by Ionis
Premature CVD with elevated Lp(a)
Nearly one-third
Share of people with premature cardiovascular disease who have elevated Lp(a)
Lp(a) genetic determination
Approximately 90%
Proportion of Lp(a) level determined genetically, per Ionis
Lp(a) thresholds
≥70 mg/dL and ≥90 mg/dL
Overall and subpopulation Lp(a) cutoffs for primary endpoint evaluation in Lp(a)HORIZON
Announcement date
September 4, 2026
Date Ionis and Novartis announced Lp(a)HORIZON topline results
Key Terms
primary endpoint, major adverse cardiovascular events (MACE), antisense oligonucleotide (ASO), elevated lipoprotein (a) [Lp(a)], +2 more
6 terms
primary endpoint medical
"study ... did not meet its primary endpoint of reducing the risk of cardiovascular events"
The primary endpoint is the single main result a clinical study is designed to measure to decide if a treatment works, like the finish line in a race that tells you who won. Investors care because meeting or missing this goal drives regulatory decisions, future sales expectations and stock value — it turns trial data into a clear yes-or-no signal about a drug’s commercial prospects.
major adverse cardiovascular events (MACE) medical
"evaluating the effect of pelacarsen on the incidence of 4-point major adverse cardiovascular events (MACE)"
Major adverse cardiovascular events (MACE) is a medical shorthand for a group of the most serious heart- and blood-vessel related outcomes—typically heart attack, stroke, and cardiovascular death—used together as a single measure in studies and reports. Investors care because MACE rates summarize a therapy’s or device’s real-world safety and effectiveness for preventing life‑threatening events; like a single report card grade, they influence regulatory approval, prescribing, liability risk, and market adoption.
antisense oligonucleotide (ASO) medical
"Pelacarsen is an investigational antisense oligonucleotide (ASO) designed to potentially inhibit"
A short, synthetic piece of genetic material designed to bind a specific RNA message inside cells and block or change how a protein is made, acting like a sticky note on a recipe that tells the cell to skip or alter one ingredient. Investors care because antisense oligonucleotides are a targeted drug approach that can address diseases with precision, offering high upside for successful therapies but also substantial development, manufacturing and regulatory risks that affect company value.
elevated lipoprotein (a) [Lp(a)] medical
"Elevated lipoprotein (a) [Lp(a)] is an inherited, independent and causal cardiovascular disease"
guideline-directed treatments medical
"Study participants received guideline-directed treatments, including lipid lowering and antihypertensive therapies"
cardiovascular outcomes trial medical
"a pioneering cardiovascular outcomes trial, did not meet its primary endpoint"
A cardiovascular outcomes trial is a large clinical study designed to see whether a medicine or intervention affects major heart-related events such as heart attacks, strokes, hospitalization for heart failure, or death. Think of it as a long road-test that measures real-world safety and benefit for the heart rather than just short-term lab results. Investors watch these trials because their results can change a product’s approval, labeling, sales potential, and legal risk, and thus a company’s valuation.
FAQ
What did Ionis Pharmaceuticals (IONS) announce about the pelacarsen Lp(a)HORIZON trial?
Ionis reported that partner Novartis’ Phase 3 Lp(a)HORIZON trial of pelacarsen in patients with elevated Lp(a) and established cardiovascular disease did not meet its primary endpoint of reducing major cardiovascular events versus placebo.
Did pelacarsen lower Lp(a) levels in the Lp(a)HORIZON study for IONS?
Yes. Ionis states that, consistent with previous studies, substantially lower Lp(a) levels were achieved with pelacarsen in Lp(a)HORIZON, even though this did not translate into a reduction in cardiovascular events versus placebo.
How many patients were enrolled in the Lp(a)HORIZON pelacarsen trial?
The Lp(a)HORIZON trial enrolled 8,323 patients with elevated lipoprotein(a) and established cardiovascular disease in a Phase 3, randomized, placebo-controlled, double-blind, multi-center global study.
What was the primary endpoint in the Lp(a)HORIZON trial for pelacarsen?
The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization, evaluated in the overall population and a higher Lp(a) subpopulation.
What safety outcomes were reported for pelacarsen in the Lp(a)HORIZON trial?
Ionis reports that pelacarsen demonstrated an acceptable safety profile in the Lp(a)HORIZON Phase 3 cardiovascular outcomes trial, with full data to be presented at an upcoming medical congress.
How common is elevated Lp(a), the target of pelacarsen, according to Ionis (IONS)?
Ionis states that elevated Lp(a) is an inherited cardiovascular risk factor affecting approximately 20% of people worldwide and nearly one-third of those with premature cardiovascular disease, with no approved targeted treatment.
What is Novartis’ role in developing pelacarsen with Ionis Pharmaceuticals (IONS)?
Ionis discovered and conducted early development of pelacarsen. In February 2019, Novartis exercised an option to license rights to develop and commercialize pelacarsen for targeted cardiovascular therapy.
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of report (Date of earliest event reported): September 4, 2026
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Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (Section 230.405 of this
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or
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| Item 7.01 |
Regulation FD Disclosure.
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On September 4, 2026, Ionis Pharmaceuticals, Inc. (“Ionis”) issued a press release announcing that its partner, Novartis, reported that the pelacarsen Phase 3 Lp(a)HORIZON study, a pioneering cardiovascular outcomes trial, did not meet its primary endpoint of reducing the
risk of cardiovascular events, a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization, compared to placebo. A copy of the press release is furnished as
Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Item 7.01 and the exhibit attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of
1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed
incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, regardless of any general incorporation language in such filing.
| Item 8.01 |
Other Events.
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On September 4, 2026, Ionis announced that its partner, Novartis, reported that the pelacarsen Phase 3 Lp(a)HORIZON study, a pioneering cardiovascular
outcomes trial, did not meet its primary endpoint of reducing the risk of cardiovascular events, a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization,
compared to placebo. Consistent with previous studies, substantially lower lipoprotein (a) (“Lp(a)”) levels were achieved with
pelacarsen. Elevated Lp(a) is an inherited cardiovascular risk factor affecting approximately one in five people worldwide with no approved targeted treatment.
Pelacarsen demonstrated an acceptable safety profile.
The full Lp(a)HORIZON data will be presented at an upcoming medical congress.
Ionis discovered and conducted the early development of pelacarsen. In February 2019, Novartis exercised an option to license the rights to develop and
commercialize pelacarsen for targeted cardiovascular therapy.
Forward-Looking Statements
This report includes forward-looking statements regarding Ionis’ business and the therapeutic and commercial potential of pelacarsen, our commercial
medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and
effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ
materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by
Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’ programs are
described in additional detail in Ionis’ annual report on Form 10-K for the year ended December 31, 2025 and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from
Ionis. In this report, unless the context requires otherwise, “Ionis,” “Company,” “we,” “our” and “us” all refer to Ionis Pharmaceuticals, Inc., and its subsidiaries.
| Item 9.01 |
Financial Statements and Exhibits.
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(d) Exhibits.
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Exhibit No.
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Description
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99.1
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Press Release dated September 4, 2026.
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104
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Cover Page Interactive Data File (embedded within the Inline XBRL document).
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed
on its behalf by the undersigned, thereunto duly authorized.
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Ionis Pharmaceuticals, Inc.
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Dated: September 4, 2026
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By:
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/s/ Patrick R. O’Neil
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Patrick R. O’Neil
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Executive Vice President, Chief Legal Officer and General Counsel
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Exhibit 99.1
Ionis partner Novartis announces Lp(a)HORIZON Phase 3 topline results for pelacarsen in patients with elevated Lp(a) and established
cardiovascular disease (CVD)
CARLSBAD, Calif., September 4, 2026 -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) partner Novartis today announced that the pelacarsen Phase 3 Lp(a)HORIZON study, a pioneering cardiovascular outcomes
trial, did not meet its primary endpoint of reducing the risk of cardiovascular events, a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization, compared
to placebo. Consistent with previous studies, substantially lower lipoprotein (a) [Lp(a)] levels were achieved with pelacarsen. Elevated Lp(a) is an inherited cardiovascular risk factor affecting approximately one in five people worldwide with no
approved targeted treatment.
"Although pelacarsen substantially lowered Lp(a) levels consistent with previous studies, we are disappointed that this did not translate to cardiovascular
risk reduction,” said Brett P. Monia, PhD, chief executive officer, Ionis. "Lp(a)HORIZON was the first pivotal Phase 3 trial to address the question as to whether lowering Lp(a) could reduce cardiovascular risk in people with established cardiovascular disease who are already receiving optimal cardiovascular care. While the study did not meet its primary endpoint, these results provide clarity that
will meaningfully inform future cardiovascular care. Ionis continues to drive the independent commercialization of our wholly owned medicines, TRYNGOLZA®, DAWNZERA® and now ZANVASTRO™, and advance a robust pipeline of
potentially transformational medicines."
Pelacarsen demonstrated an acceptable safety profile.
The full Lp(a)HORIZON data will be presented at an upcoming medical congress.
Ionis discovered and conducted the early development of pelacarsen. In February 2019, Novartis exercised an option to license the rights to develop and
commercialize pelacarsen for targeted cardiovascular therapy.
About pelacarsen
Pelacarsen is an investigational antisense oligonucleotide (ASO) designed to potentially inhibit lipoprotein(a) [Lp(a)] production at its source.
About Elevated Lp(a)
Elevated lipoprotein (a) [Lp(a)] is an inherited, independent and causal cardiovascular disease (CVD) risk factor. Lp(a) levels are approximately 90%
genetically determined and largely unaffected by diet or lifestyle. Lp(a) can contribute to plaque buildup and inflammation in the arteries, which can lead to plaque rupture and cardiovascular events. Approximately 20% of people worldwide, and nearly
one-third of those with premature cardiovascular disease, have elevated Lp(a). U.S. and European guidelines recommend Lp(a) testing once in a lifetime for all adults.
About Lp(a)HORIZON
Lp(a)HORIZON (NCT04023552) is a Phase 3, randomized, placebo-controlled, double-blind, parallel-group, multi-center global cardiovascular outcomes trial
evaluating the effect of pelacarsen on the incidence of 4-point major adverse cardiovascular events (MACE) in 8,323 patients with elevated Lp(a) and established CVD. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial
infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization, evaluated in the overall population (Lp(a) ≥70 mg/dL) and subpopulation (Lp(a) ≥90 mg/dL). Study participants received guideline-directed treatments,
including lipid lowering and antihypertensive therapies.
About Ionis Pharmaceuticals, Inc.
For more than three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines
and a leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene
editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram.
Ionis Forward-looking Statements
This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of pelacarsen, our commercial
medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and
effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ
materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by
Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are
described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2025 and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from
the Company.
In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its
subsidiaries.
Ionis Pharmaceuticals®, TRYNGOLZA®, DAWNZERA® and ZANVASTRO™ are trademarks of Ionis Pharmaceuticals, Inc.
Ionis Investor Contact:
D. Wade Walke, Ph.D.
IR@ionis.com
760-603-2331
Ionis Media Contact:
Hayley Soffer
media@ionis.com
760-603-4679