Akcea Therapeutics, Inc. announced that results from a Phase 2 study evaluating AKCEA-APO(a)-LRx, also known as TQJ230, in patients with established cardiovascular disease (CVD) and elevated levels of lipoprotein(a), or Lp(a), were published in The New England Journal of Medicine (NEJM). The article is titled “Lipoprotein(a) Reduction in Persons with Cardiovascular Disease. Elevated Lp(a) is an independent, genetic risk factor for CVD that cannot be well controlled with lifestyle modifications such as diet or exercise or with treatment using existing lipid-lowering therapies. It is estimated that there are more than eight million patients living with CVD and elevated levels of Lp(a) worldwide. AKCEA-APO(a)-LRx was discovered by Ionis and co-developed through Phase 2 by Akcea and Ionis. It is an antisense medicine developed using Ionis’ advanced LICA technology designed to inhibit the production of apolipoprotein(a) and thus reduce Lp(a) levels. Following treatment, patients experienced significant dose-dependent reductions in Lp(a) at all dose levels studied with up to an 80% reduction in Lp(a) at the highest cumulative dose regimen (equivalent to 80 mg monthly). Approximately 98% of patients at the 80 mg monthly dose regimen achieved Lp(a) levels below 125 nmol/L (50 mg/dL). Significant dose-dependent reductions in LDL-C, apoB, OxPL-apoB and OxPL-apo(a) from baseline were also observed. The majority of adverse events were mild or moderate, with the most frequent adverse events being injection site reactions (ISRs). ISRs occurred in 27% and 6% of patients on treatment and those on placebo, respectively, and were mostly mild. One patient discontinued treatment due to an ISR. There were no differences in platelet counts, liver and renal parameters, or flu-like symptoms in patients administered AKCEA-APO(a)-LRx. The randomized, double-blind, placebo-controlled, dose-ranging study of 286 patients across five countries with established CVD and elevated Lp(a) is the largest ever conducted specifically for people with elevated Lp(a). It is also the largest and longest study to date evaluating the Ionis LICA technology platform, with patients treated for up to 1 year and all patients treated for a minimum of six months. The goal was to assess the safety and tolerability of AKCEA-APO(a)-LRx and inform the dose and dose frequency for the planned Phase 3 cardiovascular outcomes study, being led by Novartis. Patients were administered AKCEA-APO(a)-LRx (20, 40 or 60 mg every 4 weeks, 20 mg every 2 weeks, or 20 mg every week) or placebo subcutaneously for six to 12 months. AKCEA-APO(a)-LRx is an antisense drug that uses Ionis’ advanced LIgand Conjugated Antisense, or LICA, technology. AKCEA-APO(a)-LRx inhibits the production of apolipoprotein(a), or apo(a), protein, thereby reducing Lp(a). The Phase 2 study was designed to evaluate the safety and tolerability of AKCEA-APO(a)-LRx and to determine the appropriate dose and dose regimen for the currently ongoing Phase 3 cardiovascular outcomes study being led by Novartis. The randomized, double-blind, placebo-controlled, dose-ranging Phase 2 study included 286 patients with established cardiovascular disease (CVD) and high Lp(a) levels (baseline mean of 90 mg/dL [225 nmol/L]- more than three times the upper limit of normal). Results from the study showed statistically significant dose-dependent reductions of Lp(a) compared to placebo at all dose levels, including low monthly doses of AKCEA-APO(a)-LRx. In the Phase 2 study, 98% of patients in the 20 mg weekly cohort and 81% of patients in the 60 mg every 4 weeks cohort achieved clinically significant reductions in Lp(a) levels bringing them below the recommended threshold of risk for CVD events (<50 mg/dL). Treatment with AKCEA-APO(a)-LRx was associated with decreases in LDL-C, apoB, OxPL-apoB, OxPL-apo(a). Most adverse events were mild. The most frequent adverse events were injection site reactions (ISRs). ISRs occurred in 27% of patients and were mostly mild with one patient discontinuing due to an ISR. There were no safety concerns related to platelet counts, liver function or renal function. Approximately 90% of patients completed treatment and the rate of discontinuation was comparable between the active and placebo groups. All patients were treated for at least six months, with some patients treated up to one year.