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 was 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 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
- 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 potential future development of AKCEA-ANGPTL3-LRx,” said Louis O’Dea, chief medical officer at
AKCEA-ANGPTL3-LRx is an investigational antisense therapy being developed to treat patients with certain cardiovascular and metabolic diseases. This antisense medicine 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-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.1 In a Phase 1/2 study, patients treated with AKCEA-ANGPTL3-LRx achieved robust, dose-dependent reductions of ANGPTL3, triglycerides, LDL-cholesterol and total cholesterol with a positive safety and tolerability profile.2 AKCEA-ANGPTL3-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis.
As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardiovascular, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.
AKCEA AND IONIS FORWARD-LOOKING STATEMENT
This press release includes forward-looking statements regarding the business of Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. and the therapeutic and commercial potential of AKCEA-ANGPTL3-LRx. Any statement describing Akcea’s or Ionis’ goals, expectations, financial or other projections, intentions or beliefs, including the commercial potential of AKCEA-ANGPTL3-LRx or other of Akcea’s or Ionis’ drugs in development is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Akcea’s and Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Akcea’s and Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Akcea and Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Akcea’s and Ionis’ programs are described in additional detail in Akcea’s and Ionis’ quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the
In this press release, unless the context requires otherwise, “Ionis,” “Akcea,” “Company,” “Companies,” “we,” “our,” and “us” refers to Ionis Pharmaceuticals and/or
Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics®, TEGSEDI® and WAYLIVRA® are trademarks of Akcea Therapeutics, Inc.
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- JAMA Cardiol. 2018
- N Engl J Med. 2017 Jul 20;377(3):222-232.