Akcea, Ionis report positive phase 2 study results of AKCEA-ANGPTL3-LRx

Boston: Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. recently 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 of significant triglyceride-lowering and multiple secondary endpoints with a favourable safety and tolerability profile. AKCEA-ANGPTL3- LRx is an investigational antisense oligonucleotide therapy being developed to treat patients with certain cardiovascular and metabolic diseases.

The objective of the dose-ranging Phase 2 study was to evaluate the safety and efficacy of AKCEA-ANGPTL3-LRx. 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. Weekly and monthly dosing were explored in three cohorts with doses ranging from 40 mg to 80 mg of total monthly dose. Observations from the AKCEA-ANGPTL3-LRx study included:

• 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
• No reductions in liver fat or haemoglobin A1C compared to placebo
• AKCEA-ANGPTL3-LRx was generally well-tolerated and demonstrated a favourable safety and tolerability profile. The most common adverse event was injection site reactions, which were mostly mild
• Changes in platelets were similar between placebo and treated groups

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. We are very grateful to the patients, families, and physicians who participated in this study and are pleased to share the data with Pfizer, who will determine strategies for the potential future development of AKCEA-ANGPTL3-LRx," said Louis O'Dea, chief medical officer at Akcea Therapeutics.

"This Phase 2 study further validates the advantages of the LICA technology platform for large indications like cardiovascular disease. We are pleased that we continue to see consistent performance with low volume monthly doses across our LICA programs in terms of efficacy, safety and patient tolerability."