Following Positive Phase II Results, Akcea to Turn Hypertriglyceridemia Asset Over to Pfizer


Akcea Therapeutics and its parent company Ionis Pharmaceuticals reported that its mid-stage trial in patients with hypertriglyceridemia, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) met the primary endpoint of significant triglyceride-lowering and multiple secondary endpoints.

The company said the Phase II asset, AKCEA-ANGPTL3-L, also met with a favorable safety and tolerability profile. AKCEA-ANGPTL3- L is an investigational antisense oligonucleotide therapy being developed to treat patients with certain cardiovascular and metabolic diseases. It is 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-L was developed using Ionis’ advanced LIgand Conjugated Antisense (LICA) technology platform. In a Phase I/II study, patients treated with AKCEA-ANGPTL3-L achieved robust, dose-dependent reductions of ANGPTL3, triglycerides, LDL-cholesterol and total cholesterol with a positive safety and tolerability profile.

The Phase II multicenter, randomized, double-blind, placebo-controlled, dose-ranging study included 105 patients with hypertriglyceridemia, type 2 diabetes and NAFLD. Participants 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. Also, AKCEA-ANGPTL3-L demonstrated Dose-dependent reductions in ANGPTL3, apoC-III, very low-density lipoprotein (VLDL-C), non-HDL cholesterol and total cholesterol compared to placebo, the company said. 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, the company said.

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

“This Phase II 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,” O’Dea said in a statement.

With the Phase II results in hand, it will be up to Pfizer to determine next steps. Pfizer licensed AKCEA-ANGPTL3-L in October 2019 with a $250 million upfront payment. At the time Pfizer struck the licensing deal, Mikael Dolsten, chief scientific officer and president of Worldwide Research & Development and Medical at Pfizer, said the asset will complement the company’s clinical mid-stage internal medicine pipeline.

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