Pelacarsen failure in trial of 8,323 patients puts Lp(a)-lowering hypothesis to the test again
Key Facts
Novartis announced on September 4, 2026, that pelacarsen failed to meet the primary endpoint of the Phase 3 Lp(a)HORIZON trial, as it did not demonstrate a reduction in the risk of cardiovascular events compared with placebo. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and urgent coronary revascularization requiring hospitalization. The company said Lp(a) levels fell in patients who received the drug, but the decline did not translate into lower risk across all participants. That leaves a gap between an effect on the biomarker and proof of clinical benefit on cardiac events. Detailed results are scheduled to be presented at an American Heart Association scientific session on November 7.
The study included 8,323 patients with elevated Lp(a) levels and established cardiovascular disease. It was a global, randomized, double-blind, placebo-controlled trial with a multicenter, parallel-group design. Novartis defined elevated Lp(a) as 70 mg/dL or higher for the overall group and 90 mg/dL or higher for the subgroup. The company said participants were receiving guideline-recommended therapies, including lipid-lowering treatment and treatment for high blood pressure. This meant pelacarsen was tested on top of existing risk-factor care, with the central question being whether lowering Lp(a) would add a benefit on cardiac outcomes.
Pelacarsen, an investigational antisense drug, was designed to inhibit the production of lipoprotein(a) at its source. Elevated Lp(a) is a genetic risk factor for cardiovascular disease, and Novartis estimates it affects about one in five people worldwide. The American Heart Association also says about 1 in 5 people worldwide have elevated levels of the marker, which is largely inherited. The association recommends that every adult be screened at least once in their lifetime, noting that a standard lipid panel does not include Lp(a). According to Novartis, there is no approved treatment specifically targeting this risk factor, making the trial result relevant to efforts to address a risk not covered by conventional lipid testing.
Shreeram Aradhye, Novartis's chief medical officer, said the results were "not what we had hoped for," but added that the data "reinforce scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes." In its third-quarter results update, the company said HORIZON data provide new evidence on this relationship and may help guide future approaches to cardiovascular risk management. The company's update had said the data would be presented at an upcoming medical conference without specifying a date in that update. The American Heart Association's program now lists the results session for Saturday, November 7, from 9:30 to 10:45 a.m. The association's 2026 scientific meetings will be held November 6 to 9 at McCormick Place in Chicago.
Novartis shares fell more than 3% on Monday, September 7, after the announcement that pelacarsen had failed, according to Investing.com. EL7 data show the stock closed at $161.1 on October 29 and then at $160.79 on October 30, 2026. These prices do not establish that the move that day was related to the trial failure, which was announced in September. The October 30 close is a separate timestamp from the reaction recorded after the announcement. The direct market impact is therefore centered on the decline reported on September 7, while EL7 data do not attribute the late-October move to the news.
Amgen is also conducting the Phase 3 OCEAN(a)-PreEvent trial for primary prevention, enrolling patients with elevated Lp(a) and a high risk of a first major cardiovascular event. Its stated scope differs from Lp(a)HORIZON, which included patients who already had established cardiovascular disease. The available information provides no result from Amgen's trial, so it remains a reference to another research program targeting the same risk factor. The next near-term milestone for Novartis data is the HORIZON presentation on November 7. The presentation will put the trial details before the medical community after the company announced that lowering the marker did not demonstrate a reduction in risk across all participants.