The primary endpoint of lowering triglycerides was met in the phase 2 study evaluating AKCEA-APOCIII-Lrx in patients with hypertriglyceridemia with high risk or established CVD. In addition, multiple secondary endpoints were met and AKCEA-APOCIII-Lrx appeared to be safe and well-tolerated.

The objective of this phase 2 study was to evaluate the safety and efficacy of different doses and dosing frequencies of AKCEA-APOCIII-Lrx. 114 Patients with CVD or high risk of CVD, who had a mean triglyceride baseline level of 285 mg/dL, were enrolled in this multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial. Patients were randomized to subcutaneous injection of AKCEA-APOCIII-Lrx or placebo for at least 6 month (some patients were treated up to one year). Dosing frequency was explored in four cohort with doses ranging from 10 mg to 50 mg of total dose per month.

Study results were:

• AKCEA-APOCIII-Lrx significantly dose-dependently reduced fasting triglyceride levels compared to placebo for all doses
• For the highest dose of 50 mg, >90% of patients achieved triglyceride levels of ≤150 mg/dL vs. <5% in the placebo group.
• Significant reductions in apoC-II, VLDL-c and remnant cholesterol and significant increase in HDL-c were observed with AKCEA-APOCIII-Lrx compared to placebo.
• Adverse events were comparable between groups. Most common adverse event in the AKCEA-APOCIII-Lrx group was injection site reactions.
• AKCEA-APOCIII-Lrx appeared to be safe
• ~85% of patients completed treatment and discontinuation rate was similar between groups.

AKCEA-APOCIII-Lrx is a ligand conjugated antisense drug, designed to reduce the production of apoC-III. ApoC-III regulates levels of serum triglycerides. Genetically low levels of apoC-II are associated with lower levels of triglycerides and lower risk of CVD. In contrast, higher levels of apoC-III are associated with high triglyceride levels, that in its turn are associated with insulin resistance and/or metabolic syndrome, as well as increased CVD risk.

Source: Press release Akcea Therapeutics, January 22, 2020