Akcea Therapeutics along with its parent company, Ionis Pharmaceuticals, announced 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 and multiple secondary endpoints.
The Phase II multicenter, randomized, double-blind, placebo-controlled, dose-ranging study included 105 patients with hypertriglyceridemia, type 2 diabetes and NAFLD. Patients were administered AKCEA-ANGPTL3-L or placebo via subcutaneous injection for six months. Weekly and monthly dosing were also explored in three cohorts in the trial.
Trial results showed statistically significant dose-dependent reductions in fasting triglycerides compared to placebo at all dose levels. AKCEA-ANGPTL3-L also demonstrated dose-dependent reductions in ANGPTL3, apoC-III, very low-density lipoprotein (VLDL-C), non-HDL cholesterol and total cholesterol compared to placebo. The most common adverse event was injection site reactions, which were mostly mild.
The company intends to present detailed results from this study at a future medical congress.
Akcea and Pfizer closed a worldwide exclusive licensing agreement in November of 2019 for AKCEA-ANGPTL3-LRx. Under terms of the agreement 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.
AKCEA-ANGPTL3-LRx is an 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. AKCEA-ANGPTL3-LRx was developed using Ionis’ advanced LIgand Conjugated Antisense (LICA) technology platform. The potential therapeutic benefits of ANGPTL3 reduction are supported by the discovery 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.