Targets apolipoprotein(a) messenger RNA, reducing apolipoprotein(a) production. Source
Adults with established cardiovascular disease and screening Lp(a) at least 70 mg/dL.
Study contextCurrent approval status is not summarized in this therapy record. A trial phase or a brand name does not establish approval for this use.
Status & indicationsPrimary cardiovascular composite: HR 1.02 (95% CI 0.9–1.15). Cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or urgent coronary revascularization requiring hospitalization.
Lp(a)HORIZON · Phase 3 · Trial investigator-institution report · 80 mg subcutaneous injection monthly · Guideline-based secondary prevention; risk-factor treatment optimized when needed before randomization. · Median follow-up: 4.7 years (57 months).
Evidence & limitationsAdverse events leading to drug discontinuation: 20.6% with pelacarsen versus 7.5% with placebo. Exact safety denominators and collection window were not verified in the available primary report. Mean exposure was 3.5 versus 4.0 years.
Safety contextA next milestone is not summarized for this therapy.
Milestone detailsStudy results apply to their own population, dose and analysis. They do not establish a ranking between therapies.
Each result belongs to its own study population, dose and analysis. Open a result for its chart, comparator, safety findings and limitations.
Lp(a): 80% reduction within arm · Week 27, the six-month endpoint for weekly dosing
20 mg weekly
Established cardiovascular disease and elevated Lp(a)
Mean within-arm change in Lp(a); placebo decreased 6%.
Injection-site reactions were most common; no significant platelet, liver or kidney differences versus placebo.
Limitations: This dose-finding biomarker result is separate from the later 80 mg-monthly HORIZON outcomes regimen.
Lp(a): 77.7 percentage-point reduction vs placebo · 12 months (displayed at approximately 52 weeks)
80 mg monthly
Established cardiovascular disease and screening Lp(a) at least 70 mg/dL
Estimated treatment difference in Lp(a) reduction from baseline at 12 months, versus placebo.
Adverse-event drug discontinuation: 20.6% versus 7.5% over the trial; exact safety denominators and collection window were not verified. Mean exposure: 3.5 versus 4.0 years.
Limitations: Separate from the 2020 phase 2 20 mg-weekly regimen. This biomarker endpoint did not translate into demonstrated cardiovascular-event benefit in HORIZON. The 8,322 count is the reported efficacy population, not a verified 12-month biomarker denominator. Enrollment counts differ between the investigator report and registry/AHA; exact arm counts remain unverified.
Primary cardiovascular composite: HR 1.02 (95% CI 0.9–1.15). Cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or urgent coronary revascularization requiring hospitalization.
80 mg subcutaneous injection monthly
Adults with established cardiovascular disease and screening Lp(a) at least 70 mg/dL.
Background treatment & comparator: Guideline-based secondary prevention; risk-factor treatment optimized when needed before randomization.
Median follow-up: 4.7 years (57 months). Source reports 511 events (12.3%) versus 503 (12.1%) during median 4.7-year follow-up; exact arm denominators and the percentage-estimation method were not verified.
Adverse events leading to drug discontinuation: 20.6% with pelacarsen versus 7.5% with placebo. Exact safety denominators and collection window were not verified in the available primary report. Mean exposure was 3.5 versus 4.0 years.
Limitations: Efficacy analysis count is 8,322 in the investigator-institution report; that report gives 8,350 enrolled, while the registry and AHA give 8,323. Counts are not harmonized by assumption. Reported event percentages (12.3% versus 12.1%) are not entered into the absolute-risk plot until their crude versus Kaplan-Meier basis and exact denominators can be verified. This trial addresses this drug and regimen in secondary prevention, not all Lp(a)-lowering therapies or primary prevention.
Status in this atlas: Current approval status is not summarized in this therapy record. A trial phase or a brand name does not establish approval for this use.
Targets apolipoprotein(a) messenger RNA, reducing apolipoprotein(a) production.
Mechanism sourceUses, doses and availability depend on the formulation, indication and country. Study doses below describe research; they are not prescribing instructions.
Hepatocyte-targeted antisense oligonucleotide with a three-arm GalNAc conjugate.
Shown: GalNAc-conjugated antisense oligonucleotide (TQJ230; IONIS-APO(a)-LRx).
This is the GalNAc-conjugated pelacarsen compound, distinct from its earlier unconjugated predecessor. No exact whole-drug atomic model has been verified for this bundle.
DOI 10.1111/cts.70344Pelacarsen · compound history across indications
Selected pelacarsen milestones and the November 7 HORIZON full report were reviewed; the earlier 2016 human study and 2020 phase 2 result remain distinct. History is not exhaustive and other profiles were not refreshed. Focused program-status reconciliation completed November 11: recovered October 16 discontinuation letter and November 10 extension registry, while preserving previous results.
Akcea announced Lancet publication of the first human study of the liver-targeted compound later named pelacarsen. Multiple doses lowered Lp(a); the publication also covered its earlier, unconjugated predecessor, which is a distinct compound.
Akcea announces Lancet clinical results for IONIS-APO(a)-LRx (2016)The registry records the actual start of the phase 3 trial testing whether pelacarsen reduces cardiovascular events in patients with established cardiovascular disease and elevated Lp(a).
ClinicalTrials.gov: Lp(a)HORIZON, NCT04023552The plotted dose-ranging trial in 286 patients with cardiovascular disease reported dose-dependent Lp(a) lowering, reaching a mean 80% reduction at the highest tested regimen. This was a biomarker study, not an outcomes trial.
Lipoprotein(a) Reduction in Persons with Cardiovascular Disease — NEJM (2020)Novartis announced that the phase 3 cardiovascular composite was not met despite lower Lp(a). The announcement did not provide a hazard ratio or confidence interval; full results were pending.
Novartis: Lp(a)HORIZON phase 3 topline results (September 4, 2026)Novartis’s original patient-community letter, dated October 16 and shared publicly by FH Europe Foundation November 2, discontinues the pelacarsen ASCVD clinical-development program after HORIZON. Newly recovered in the November 10 scheduled review; it does not stop all Lp(a) programs.
Original Novartis patient-community statement, October 16, 2026The AHA report and simultaneous NEJM publication provide numerical results after September's negative topline. In the investigator report, the primary cardiovascular composite had HR 1.02 (95% CI 0.90-1.15) at median 4.7-year follow-up despite an estimated 77.7% placebo-adjusted Lp(a) reduction at 12 months. Adverse-event drug discontinuation was 20.6% versus 7.5%. This was secondary prevention; results do not establish effects of other Lp(a) drugs or primary prevention.
Lp(a)HORIZON investigator report, November 7, 2026NCT05900141 now lists sponsor termination following the parent trial’s missed endpoint, 41 actually enrolled and October 15 actual completion. Posting date is not first dosing, the program-decision date, or a new safety outcome.
ClinicalTrials.gov: pelacarsen open-label extension, update November 10, 2026Selected sources checked Nov 11, 2026. This is not an exhaustive history.