Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. announced positive topline results from the Phase 2 study of AKCEA-APOCIII-LRx in the treatment of patients with hypertriglyceridemia who are at risk for or have established cardiovascular disease (CVD). The study met the primary endpoint of significant triglyceride lowering and multiple secondary endpoints with a favorable safety and tolerability profile. The objective of the Phase 2 study was to evaluate the safety and efficacy of different doses and dosing frequencies of AKCEA-APOCIII-LRx.

The multicenter, randomized, double-blind, placebo-controlled, dose-ranging study included 114 patients with a clinical diagnosis of CVD or who are at high risk of CVD. Participants were administered AKCEA-APOCIII-LRx or placebo via subcutaneous injection for at least six months with some patients being treated up to a year. Weekly, bi-weekly, and monthly dosing was explored in four cohorts with doses ranging from 10 mg to 50 mg of total monthly dose.

Observations from the AKCEA-APOCIII-LRx study included: Statistically significant dose-dependent reductions in fasting triglycerides compared to placebo at all dose levels. At the high once monthly dose of 50 mg, more than 90% of patients achieved serum triglycerides of = 150 mg/dL, compared to less than 5% of patients in the placebo group; mean triglyceride levels of patients at baseline was 285 mg/dL Significant reductions in multiple additional risk factors, including apoC-III, very low-density lipoprotein (VLDL-C) and remnant cholesterol, compared to placebo; Statistically significant increases in high-density lipoprotein cholesterol (HDL-C) compared to placebo at all dose levels; Treatment-emergent adverse events (TEAEs) were comparable between active and placebo groups. The most common adverse event was injection site reactions (ISRs).

ISRs were mostly mild, infrequent and primarily occurred in the weekly dose group. In the high monthly dose group, the occurrence of ISRs was similar to the placebo group; There were no safety signals, including those related to platelet counts, liver function or renal function; Approximately 85% of patients completed treatment and the rate of treatment discontinuation was comparable between the active and placebo groups. AKCEA-APOCIII-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis.

It is an antisense drug developed using Ionis' proprietary LIgand Conjugated Antisense (LICA) technology platform and is designed 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.