CAMBRIDGE, Mass. and CARLSBAD, Calif. ,
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  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.
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ABOUT IONIS PHARMACEUTICALS, INC.
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 www.ionispharma.com.
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