Heart Drug Failure: Pelacarsen Trial Data Dims Prospects for Rival Lp(a) Treatments

The pharmaceutical industry is reevaluating its approach to treating elevated lipoprotein(a) levels after detailed data from a major clinical trial revealed that a leading candidate did not prevent heart attacks or strokes. The publication of the full results for pelacarsen on Sunday confirmed that the drug, while effective at lowering the target biomarker, failed to reduce the risk of major adverse cardiovascular events over a five-year period.

Novartis, which partnered with Ionis Pharmaceuticals in 2019 to develop the once-monthly injection, disclosed in September that the Horizon Phase 3 trial had not met its primary endpoint. Ionis shares fell 17.8% in premarket trading on Monday, a drop attributed to both the trial data and third-quarter earnings that included lowered sales guidance for the company’s drug Tryngolza. In contrast, Novartis shares listed in Switzerland rose approximately 1% on the news. Ionis stock closed at $38.80 on Thursday, marking its lowest point of the year compared to a high of $86.50 reached on Feb. 6.

Pelacarsen is an antisense oligonucleotide designed to block the production of proteins that can damage the heart. Lp(a) is an inherited substance similar to bad cholesterol, and it cannot be lowered by diet or statins. Scientists previously believed that reducing Lp(a) levels would lead to fewer serious cardiac events, a view one researcher called the next frontier in cardiovascular disease in 2025. The Horizon data challenged this assumption by showing no clear reduction in major cardiovascular events despite the drop in Lp(a).

The failure casts a shadow over other companies pursuing therapies based on the same biological mechanism. Eli Lilly’s lepodisiran and Amgen’s olpasiran are currently in Phase 3 studies. Analysts had projected that olpasiran alone could generate $2.3 billion in peak sales by 2036. The new data has prompted investors to question whether these rival programs will succeed in proving their benefits.

Evan David Seigerman, an analyst at BMO Capital Markets, told investors on Sunday that the Horizon results call the trial designs of other Lp(a) focused programs into question. He stated that the probability of olpasiran or lepodisiran demonstrating a clear benefit in secondary prevention for patients with well-controlled LDL-C is extremely low based on the published findings. Novartis has confirmed it will no longer develop pelacarsen, according to reports from Bloomberg.

The market reaction underscores the high stakes involved in targeting this specific cardiovascular risk factor. As investors process the implications of the Horizon trial, the focus shifts to how Eli Lilly and Amgen respond to the data and whether their ongoing studies will show different outcomes in their respective patient populations.