Lp(a)FRONTIERS APHERESIS: pelacarsen replaces lipoprotein apheresis in 25 of 26 patients (Parhofer et al., EHJ 2026)

Original title: Pelacarsen and lipoprotein(a) apheresis in secondary prevention: the Lp(a)FRONTIERS APHERESIS trial

Eur Heart J · 1 July 2026 · 9

Parhofer KG, Julius U, Herzog AL, Krüger T, Weinmann-Menke J, Heine GH, Cao H, Schorr J, Ferber P, Wang J, Cristante E, Müller-Edenborn B et al.

The first phase 3 result for pelacarsen: 51 German patients with Lp(a) above 60 mg/dL and established CVD on weekly apheresis (mean 44 sessions in the prior year) received pelacarsen 80 mg or placebo every 4 weeks for 52 weeks, with apheresis performed only when Lp(a) stayed above 60 mg/dL. Pelacarsen cut the rate of apheresis sessions to 0.16 versus 0.93 of the weekly schedule, achieved apheresis avoidance after a median 6.1 weeks (hazard ratio 88), and lowered Lp(a) by 72 percent at week 52, with mild injection-site erythema in 38 percent as the only difference in adverse events.

Original abstract

Background And Aims: Lipoprotein apheresis (LA) is the only approved treatment for patients with elevated lipoprotein(a) [Lp(a)]. The Lp(a)FRONTIERS APHERESIS trial investigated whether pelacarsen reduces the need for LA in patients from Germany with elevated Lp(a) and established cardiovascular disease (CVD).

Methods: Adult patients with Lp(a) levels >60 mg/dl who had undergone ≥35 LA sessions in the prior year were randomized to receive pelacarsen 80 mg or placebo every 4 weeks for 52 weeks. Weekly LA sessions were performed if the Lp(a) measurement from the prior visit was >60 mg/dL. The primary endpoint was the rate of performed LA sessions normalized to the weekly LA schedule (the number of actual LA sessions divided by the number of planned LA sessions during the 52-week period). Secondary endpoints were time to LA avoidance (for ≥24 consecutive weeks) and total LA avoidance from week 12 to week 52.

Results: Fifty-one patients were randomized (mean age 61.7 years, mean Lp(a) at baseline 85.4 mg/dL, and mean 44.0 LA sessions in the past 12 months), with 25 of 26 (96.2%) in the pelacarsen arm and 23 of 25 (92.0%) in the placebo arm completing the study. Baseline characteristics were generally balanced between treatment arms. Pelacarsen reduced the mean rates of LA (0.16 vs 0.93 in placebo, odds ratio 0.006, 95% confidence interval [CI] 0.003, 0.013; P < .0001) and substantially increased the hazard of achieving LA avoidance (hazard ratio: 88.3; P = .0014; median time to achieve LA avoidance: 6.1 weeks) and total LA avoidance (odds ratio: 163.2; P = .0005). The placebo-adjusted Lp(a) change from baseline at week 52 was -72% (95% CI: -79%, -61%; P < .0001). Treatment emergent adverse events were similar between arms, except for mostly mild injection site erythema (pelacarsen 38.5%; placebo 0%).

Conclusions: Pelacarsen is a highly effective and well-tolerated Lp(a)-targeted therapy that substantially reduces the need for LA in patients with elevated Lp(a) and established CVD.

Clinicaltrials.Gov, Identifier: NCT05305664.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.