Positive Phase 1/2 Results of AKCEA-APOCIII-LRx Presented at American College of Cardiology Annual Scientific Session & Expo

CAMBRIDGE, Mass. and CARLSBAD, Calif. , March 12, 2018 (GLOBE NEWSWIRE) -- Akcea Therapeutics, Inc. (NASDAQ:AKCA), an affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ:IONS), and Ionis Pharmaceuticals, Inc., today announced the presentation of a poster summarizing results from the completed Phase 1/2 clinical study of AKCEA-APOCIII-LRx at the American College of Cardiology (ACC) Annual Scientific Session & Expo on March 10, 2018, in Orlando, Florida.



AKCEA-APOCIII-LRx, an antisense drug that uses Ionis’ advanced LIgand Conjugated Antisense (LICA) technology. It is designed to reduce the production of apolipoprotein C-III, or apoC-III, for the broad population of patients who have cardiometabolic disease due to their elevated triglyceride levels and ApoC-III.

 Phase 1/2 Study Results:

  • A total of [67] healthy volunteers and patients with elevated triglycerides were treated with multiple doses of AKCEA-APOCIII-LRx
  • Treatment resulted in significant, dose-dependent reductions in ApoC-III protein of up to 84% after six weeks of treatment and in triglycerides of up to 71%.
  • Significant dose-dependent reductions of up to 30% in apolipoprotein B (apoB) and increases of up to 100% in high-density lipoprotein cholesterol (HDL-C) were also observed. Both decreased levels of apoB and increased levels of HDL-C are associated with decreased cardiovascular risk.
  • ApoC-III protein levels remained reduced by up to 50% for ~90 days after the last dose. 
  • There were no serious adverse events or adverse events leading to treatment discontinuation. There were no hepatic or renal signals, injection site or flu-like reactions and no clinically significant findings in routine hematology or biochemistry, including no platelet reductions.

To view the poster and full study results, please click here.

“We are pleased to share the outcomes of this AKCEA-APOCIII-LRx study with the ACC community. The data showing significant and sustained reductions of multiple parameters, including ApoC-III and triglyceride levels, underscore the important regulatory role ApoC-III protein plays in controlling lipid levels in blood, and the potentially broad implications that reducing ApoC-III levels could have for cardiovascular health. We look forward to seeing the results from our AKCEA-APOCIII-LRx Phase 2 study in 2019,” said Dr. Louis O’Dea, chief medical officer at Akcea Therapeutics.

The poster is titled “Inhibition of Apolipoprotein C-III With GalNAc Conjugated Antisense Drug Potently Lowers Fasting Serum Apolipoprotein C-III and Triglyceride Levels in Healthy Volunteers With Elevated Triglycerides.” As previously reported, the clinical study enrolled healthy volunteers and patients with elevated triglyceride levels. In single ascending, sequential dose cohorts, 10, 30, 60, 90, or 120 mg were given subcutaneously. In multiple ascending dose cohorts, 2 groups were given 15 or 30 mg weekly subcutaneously for 6 weeks and 1 group was given 60 mg every 4 weeks subcutaneously for 3 months. 

Based on the positive results of this Phase 1/2 study, AKCEA-APOCIII-LRx is now being investigated in a Phase 2 clinical study in approximately 100 patients with hypertriglyceridemia and established cardiovascular disease (CVD). The study will evaluate the safety and efficacy of different doses and dosing frequencies of AKCEA-APOCIII-LRx in this patient population. Akcea anticipates reporting top-line data from this study in 2019.

AKCEA-APOCIII-LRx is part of a strategic collaboration with Novartis to develop and co-commercialize AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx. Under the terms of the collaboration, if Novartis exercises its option after successful completion of the Phase 2 study, it will be responsible for a global Phase 3 cardiovascular outcome study as well as worldwide development and, if approved, global co-commercialization activities.

AKCEA-APOCIII-LRx is a ligand conjugated antisense (LICA) drug designed to reduce the production of apolipoprotein C-III, or apoC-III. ApoC-III is a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Genetically reduced levels of apoC-III are correlated to lower levels of triglycerides and lower risk of cardiovascular disease whereas elevated levels of apoC-III correlate with high triglyceride levels that have been associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. Akcea and Ionis are developing AKCEA-APOCIII-LRx to treat hypertriglyceridemia and established cardiovascular disease.

AKCEA-APOCIII-LRx utilizes Ionis’ LICA technology, which conjugates specific chemical structures or molecules to antisense drugs to increase the efficiency of drug uptake in a particular tissue. The enhancements from the LICA technology have the potential to allow for less frequent administration and significantly lower doses, providing greater patient convenience. Phase 1 studies of all three of Akcea’s LICA drugs have shown that doses up to 30-fold lower than non-LICA drugs result in consistent target reductions and a favorable safety and tolerability profile.

In January 2017, Akcea and Ionis entered into an exclusive, worldwide option and collaboration agreement with Novartis to develop and commercialize AKCEA-APOCIII-LRx and AKCEA-APO(a)-LRx. Akcea plans to complete the ongoing Phase 2 dose-ranging study for AKCEA-APO(a)-LRx in patients with high lipoprotein(a), or Lp(a), with established cardiovascular disease and the ongoing Phase 2 dose-ranging study for AKCEA-APOCIII-LRx in patients with hypertriglyceridemia and established cardiovascular disease. Both studies are being conducted to choose the optimal dose and evaluate alternative dose schedules, such as monthly dosing, for Phase 3 cardiovascular outcomes studies. Following the successful completion of each Phase 2 dose-ranging study, and prior to initiation of the Phase 3 study, Novartis has the option to license and commercialize each drug. For each drug, upon option exercise, Novartis will pay Akcea a $150 million license fee of which 50% will be paid to Ionis. Upon licensing, Novartis plans to conduct a global Phase 3 cardiovascular outcome study in high-risk patients. Novartis will be responsible for worldwide development and, if approved, co-commercialization activities. Akcea retains the right to co-commercialize any successful drug through its specialty sales force focused on lipid specialists on terms and conditions to be agreed with Novartis.  

Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals, Inc., is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with serious cardiometabolic diseases caused by lipid disorders. Akcea is advancing a mature pipeline of four novel drugs, including volanesorsen, AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx and AKCEA-APOCIII-LRx, all with the potential to treat multiple diseases. All four drugs were discovered by and are being co-developed with Ionis, a leader in antisense therapeutics, and are based on Ionis’ proprietary antisense technology. The most advanced drug in its pipeline, volanesorsen, is under regulatory review in the U.S., EU and Canada for the treatment of familial chylomicronemia syndrome, or FCS, and is currently in Phase 3 clinical development for the treatment of familial partial lipodystrophy, or FPL. Akcea is building the infrastructure to commercialize its drugs globally with a focus on lipid specialists as the primary call point. Akcea is located in Cambridge, Massachusetts. Additional information about Akcea is available at


Ionis is the leading company in RNA-targeted drug discovery and development focused on developing drugs for patients who have the highest unmet medical needs, such as those patients with severe and rare diseases. Using its proprietary antisense technology, Ionis has created a large pipeline of first-in-class or best-in-class drugs, with over three dozen drugs in development. SPINRAZA® (nusinersen) has been approved in global markets for the treatment of spinal muscular atrophy (SMA). Biogen is responsible for commercializing SPINRAZA. Drugs that have successfully completed Phase 3 studies include inotersen, an antisense drug Ionis is developing to treat patients with hereditary TTR amyloidosis (hATTR), and volanesorsen, an antisense drug discovered by Ionis and co-developed by Ionis and Akcea Therapeutics to treat patients with either familial chylomicronemia syndrome or familial partial lipodystrophy. Akcea, an affiliate of Ionis, is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with serious cardiometabolic diseases caused by lipid disorders. If approved, volanesorsen will be commercialized through Ionis' affiliate, Akcea. Inotersen filings for marketing approval have been submitted in the U.S. and EU. Volanesorsen filings for marketing approval have been submitted in the U.S., EU, and Canada. Ionis' patents provide strong and extensive protection for its drugs and technology. Additional information about Ionis is available at

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-APOCIII-LRx and other products in development. Any statement describing Akcea’s or Ionis’ goals, expectations, financial or other projections, intentions or beliefs 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 their most recent annual report on Form 10-K for the year ended December 31, 2017, which are on file with the SEC.

In this press release, unless the context requires otherwise, “Ionis”, “Akcea,” “Company,” “Companies” “we,” “our,” and “us” refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.

Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics™ is a trademark of Ionis Pharmaceuticals, Inc.   

Akcea Media and Investor Contact:

Kathleen Gallagher
Executive Director, Corporate Communications and Investor Relations

Ionis Media and Investor Contact:
D. Wade Walke, Ph.D.
Vice President, Corporate Communications and Investor Relations