Rare Daily Staff

Akcea Therapeutics and parent Ionis Pharmaceuticals reported positive topline results from the phase 2 study of AKCEA-ANGPTL3-LRx in patients with hypertriglyceridemia, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD).

The study met the primary endpoint of significant triglyceride lowering and multiple secondary endpoints with a favorable safety and tolerability profile.

AKCEA-ANGPTL3-LRx is an experimental antisense therapy designed to reduce the production of angiopoietin-like 3 (ANGPTL3) protein in the liver, a key regulator of triglycerides, cholesterol, glucose and energy metabolism. Researcher have shown that ANGPTL3 reduction that people with a genetic deficiency in ANGPTL3 have reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides, and a decreased risk of diabetes and cardiovascular disease.

The multicenter, randomized, double-blind, placebo-controlled study included 105 patients with hypertriglyceridemia, type 2 diabetes and NAFLD. Participants were administered AKCEA-ANGPTL3-LRx or placebo via subcutaneous injection for six months.

Results showed statistically significant dose-dependent reductions in fasting triglycerides compared to placebo at all dose levels; dose-dependent reductions in ANGPTL3, apoC-III, very low-density lipoprotein (VLDL-C), non-HDL cholesterol and total cholesterol compared to placebo. There were no reductions in liver fat or hemoglobin A1C compared to placebo.

AKCEA-ANGPTL3-LRx was generally well-tolerated and demonstrated a favorable safety and tolerability profile. The most common adverse event was injection site reactions, which were mostly mild.

Detailed results from this study will be presented at a future medical congress.

“Results from the Phase 2 study showed that antisense-mediated reduction of ANGPTL3 has the potential to address unmet needs in patients with cardiovascular diseases,” said Louis O’Dea, chief medical officer at Akcea Therapeutics.

In November 2019, Akcea announced a worldwide exclusive licensing agreement with Pfizer for AKCEA-ANGPTL3-LRx for which Akcea and Ionis received a $250 million upfront license fee, which was split equally between the two companies. Pfizer is responsible for all development and regulatory activities and costs beyond those associated with this phase 2 study. Akcea and Ionis are also eligible to receive development, regulatory and sales milestone payments of up to $1.3 billion and tiered, double-digit royalties on annual worldwide net sales.

Photo: Louis O’Dea, chief medical officer at Akcea Therapeutics

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