Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. announced the Phase 2 study of AKCEA-APOCIII-LRx in an online Late Breaking Clinical Trial Session at the ESC Congress 2020, the annual meeting of the European Society of Cardiology. Results showed that AKCEA-APOCIII-LRx met primary and key secondary endpoints with significant reductions in triglyceride (TG) and apoC-III levels, and a favorable safety and tolerability profile in the treatment of patients with hypertriglyceridemia who have established cardiovascular disease (CVD) or are at risk for CVD.  AKCEA-APOCIII-LRx is designed using Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform to inhibit production of apolipoprotein C-III (apoC-III), a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Epidemiological studies show that apoC-III levels may help predict risk of CVD.

The Phase 2 study was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study designed to evaluate the safety, tolerability and efficacy of AKCEA-APOCIII-LRx in patients with hypertriglyceridemia and a clinical diagnosis of CVD or who are at high risk of CVD. The study was also designed to identify the optimal dose and dose regimen to lower TG, apoC-III and other lipid and lipoprotein levels for subsequent Phase 3 studies. The study involved 114 patients randomized to four cohorts and in a 4:1 ratio (treatment: placebo) within each cohort.

AKCEA-APOCIII-LRx or placebo was administered via subcutaneous injection for at least six months, with some patients treated up to a year. Weekly, bi-weekly, and monthly dosing regimens were explored with total monthly doses ranging from 10 mg to 50 mg. Data from the Phase 2 study show:Statistically significant dose-dependent reductions in fasting TGs compared to placebo at all dose levels with a 62% reduction at the highest dose (50 mg every four weeks), and with 91% of patients achieving TG levels of < 150 mg/dL (=1.7 mmol/L) at this dose at six months. Significant reductions in apoC-III (up to 74%) and atherogenic lipoproteins including very low-density lipoprotein (VLDL) cholesterol (60%), non-high-density lipoprotein (non-HDL) cholesterol (24%), and apolipoprotein B, or apoB (16%).

High-density lipoprotein (HDL) cholesterol levels increased by up to 42%. AKCEA-APOCIII-LRx demonstrated a favorable tolerability and safety profile with mild treatment-emergent adverse events at the injection site being the most frequent.