| Clinical data | |
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| Other names | AKCEA-APO(a)-LRx, IONIS-681257, TQJ230, IONIS-APO(a)-LRx, ISIS-APO(a)-LRx |
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| Legal status |
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| Identifiers | |
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| CAS Number | |
| Chemical and physical data | |
| Formula | C296H439N71O163P20S13 |
| Molar mass | 8636.36 g·mol−1 |
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Pelacarsen is an experimental antisense oligonucleotide drug designed to lower lipoprotein(a) (Lp(a)) levels in patients with cardiovascular disease. [1] The drug targets the LPA gene that encodes apolipoprotein(a), a key component of lipoprotein(a). [1] [2] [3] It was developed by Ionis Pharmaceuticals and Novartis. [4]
As of August 2025, pelacarsen is undergoing Phase 3 clinical trials to evaluate its efficacy in reducing major cardiovascular events in patients with established cardiovascular disease and elevated Lp(a) levels. [5]
Pelacarsen is a second-generation, hepatocyte-directed antisense oligonucleotide that targets the messenger RNA (mRNA) transcribed from the LPA gene. [1] The drug works by binding to the specific mRNA sequence, leading to its degradation through RNase H-mediated cleavage. [6]
The antisense oligonucleotide includes chemical modifications such as triantennary N-acetylgalactosamine conjugation, which improve biostability, decrease off-target toxicity compared with unmodified antisense oligonucleotides, and allow rapid, specific uptake by hepatocytes. [6] This results in decreased apolipoprotein(a) production and consequently lower circulating Lp(a) levels. [1]
In Phase 2 clinical trials, pelacarsen demonstrated significant reductions in Lp(a) levels. The phase 2B trial was a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening Lp(a) levels ≥60 mg/dL (≥150 nmol/L). [7]
Studies in healthy Japanese subjects showed dose-dependent reductions in Lp(a) levels, with placebo-corrected reductions of 55.4%, 58.9%, and 73.7% for 20 mg, 40 mg, and 80 mg doses, respectively, at day 30. [8]
The primary Phase 3 study is the Lp(a)HORIZON trial (NCT04023552), a global, multicenter, double-blind, placebo-controlled study conducted by Novartis. [5] The trial enrolled 8,323 patients with established cardiovascular disease and elevated Lp(a) levels of ≥70 mg/dL (approximately 149 nmol/L), testing the effect of pelacarsen on major cardiovascular events. [5] [9]
Additional Phase 3 studies include the Lp(a)FRONTIERS CAVS trial, which is assessing the impact of Lp(a) lowering with pelacarsen on the progression of calcific aortic valve stenosis. [10]
Pelacarsen is administered as a subcutaneous injection once monthly. [11] The drug has demonstrated good tolerability in clinical studies, with the ability to reduce lipoprotein(a) levels by up to 80%. [12]
Pelacarsen was initially developed by Ionis Pharmaceuticals under various developmental names including ISIS-APO(a)-LRx, IONIS-APO(a)-LRx, and AKCEA-APO(a)-LRx. [13] The drug was later licensed to Novartis, which assigned it the development code TQJ230. [13]
Pelacarsen sodium (IONIS-APOALRx) is under development for the treatment of cardiovascular diseases, aortic valve stenosis and hyperlipoproteinemia. [14] The drug currently has investigational status and has not been approved by any regulatory agency for clinical use.