Data Readout

Novartis's pelacarsen Lp(a) HORIZON outcome trial still awaits its readout past mid-2026 window

The Phase 3 cardiovascular outcomes trial closed enrollment years ago, but Novartis has not disclosed results after guiding to a mid-2026 readout, leaving the field's most advanced Lp(a)-lowering test still open.

By AppliedXLFebruary 25, 2026Trial NCT04023552

Executive Summary

A Phase 3 cardiovascular outcomes trial testing whether lowering Lp(a), a genetically driven lipid particle, reduces major cardiovascular events has not yet disclosed results, even as its sponsor guided publicly to a mid-2026 window that has now closed.
No therapy has yet proven that lowering Lp(a) itself changes cardiovascular outcomes, and this trial is the largest and most advanced attempt to answer that question before rival programs from Eli Lilly reach their own outcomes readouts.
The trial's completion timeline has moved repeatedly over its life, including a push announced earlier this year, a pattern that bears on when investors should expect the actual readout rather than on the trial's underlying design.
Direct comparators from Eli Lilly targeting the same lipoprotein are still in earlier stages of Phase 3 testing, so this trial's data will be the first cardiovascular-outcomes evidence in the class regardless of when it lands.

The catalyst

Ionis Pharmaceuticals said in a February 25, 2026 earnings release that its partner Novartis expected data from the Phase 3 Lp(a) HORIZON trial of pelacarsen in the second quarter of 2026, calling it one of two cardiovascular outcome trials on deck for the year. Ionis chief executive Brett Monia said the partnered pipeline was "on track for multiple groundbreaking Phase 3 readouts," naming the pelacarsen trial specifically for mid-2026. That stated window ran from April 1 through June 30, 2026, and closed without a disclosed result. The trial, registered as NCT04023552, tests pelacarsen, an antisense oligonucleotide that lowers Lp(a) mRNA, against placebo in 8,323 patients with established cardiovascular disease and elevated Lp(a). Ionis+1

What the trial tests

The primary endpoint is time to first clinical-endpoint-committee-confirmed expanded major adverse cardiovascular event in patients with Lp(a) of 70 mg/dL or higher, a hard-outcomes composite rather than a biomarker surrogate. The trial is randomized, double-masked, and placebo-controlled, with two arms and a registered primary completion date of June 30, 2026. Enrollment finished years ago: Novartis reported completing enrollment of 8,325 participants back in July 2022. This design, a large randomized outcomes trial with a hard composite endpoint, means the readout can speak directly to whether Lp(a) lowering changes cardiovascular risk, not merely whether it lowers the biomarker. NCT04023552

Timeline history

The registered primary completion date has moved eight times since the trial began, starting at March 1, 2024 and arriving, after a sequence of pulls forward and pushes back, at June 30, 2026. The most recent change came in February 2026, when the date moved from February 26, 2026 to June 30, 2026, a four-month push announced roughly two weeks before Ionis's earnings call named the same mid-2026 window. Enrollment counts also moved nine times across the trial's life, settling at 8,323 after fluctuating between 7,680 and 8,350. The trial's status briefly flipped from Active, not recruiting back to Recruiting in August 2022 before returning to Active, not recruiting days later. Taken together, the completion-date pattern is the more consequential signal here: it is what determines whether the currently registered date still holds as the readout's real anchor. NCT04023552+1

The competitive landscape

No therapy has established that lowering Lp(a) itself reduces hard cardiovascular outcomes, so this trial's data would be the first outcomes-level evidence for the mechanism. Eli Lilly and Company's lepodisiran, in a Phase 3 trial testing plaque reduction in patients with elevated Lp(a) and prior cardiac events, is the closest direct comparator on target and modality but remains in earlier-stage testing, according to competitive-trial screening. Eli Lilly's muvalaplin, a small-molecule Lp(a) disruptor, is also in Phase 3 but targets the same mechanism through a different modality, per that same screening. Mechanism-tier competitors targeting PCSK9, including Amgen's olpasiran, evolocumab, and Novartis's own inclisiran, work through a different pathway and are not direct substitutes for the Lp(a)-lowering hypothesis this trial is built to test.

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