Novartis and Ionis heart drug pelacarsen fails Phase 3 trial despite lowering Lp(a)

Phase 3 clinical trial outcome

On 4 September 2026, Swiss drugmaker Novartis and its partner Ionis Pharmaceuticals announced that their experimental cardiovascular drug pelacarsen failed to meet its primary objective in a Phase 3 study. The trial tested whether the monthly injection could reduce cardiovascular events in patients with established heart disease compared with a placebo. Pelacarsen did not decrease the incidence of death from heart disease, heart attacks, strokes, or the need for urgent procedures to restore blood flow to the heart. While the drug successfully lowered blood levels of the targeted cholesterol-carrying particle, this biological effect did not translate into clinical protection for patients.

Although pelacarsen substantially lowered lipoprotein(a) levels consistent with previous studies, we are disappointed that this did not translate to cardiovascular risk reduction.

Trial parameters and lipoprotein biology

The clinical study ran for seven years and enrolled 8,323 participants who had high levels of lipoprotein(a), commonly abbreviated as Lp(a), along with pre-existing heart disease. Patients in the study administered pelacarsen or a placebo once a month using pre-filled syringes. Lp(a) is a genetically determined particle that does not fluctuate over a person's lifetime and cannot be modified through diet, exercise, or lifestyle changes. Elevated Lp(a) affects an estimated 1.4 billion to 2 billion people globally, representing one in five individuals. The highest concentrations, exceeding 250 nanograms per deciliter and found in 10% of the world population, double the risk of heart attack or stroke, while slightly elevated levels increase risk by 25%.

Cardiology reactions and clinical implications

Prior to the Phase 3 findings, cardiologists anticipated that therapies reducing Lp(a) could function as a critical tool alongside statins to prevent cardiovascular incidents. Every non-randomized study had indicated that reducing the particle would protect against disease development, particularly in individuals whose blood pressure and standard cholesterol were already controlled. The announcement produced immediate reactions across the cardiology community, as specialists had prepared for positive results following years of observational evidence.

This is extremely disappointing news. We've all been looking forward to celebrating.

Dr. David Maron, president of the American College for Preventive Cardiology, expressed surprise at the outcome of the multi-year study.

This is a huge blow. I hardly know what to say.

Market impact and competing programs

Following the announcement of the trial results, shares of Ionis Pharmaceuticals dropped 6% in aftermarket trading, while Novartis shares fell 1.33%. Pelacarsen represented one of three late-stage treatments, alongside the multiple sclerosis therapy remibrutinib and the genetic medicine del-desiran, that Novartis projected to generate more than $10 billion in combined peak annual sales. The failure also affects the broader pharmaceutical sector, where companies such as Amgen and Eli Lilly are conducting large clinical trials for their own experimental drugs designed to lower Lp(a) levels.