Positive Phase 2 Clinical Data of AKCEA-APOCIII-L(Rx) Presented at ESC Congress 2020

Results in late-breaking presentation show patients with hypertriglyceridemia experienced dose-dependent reductions in triglyceride levels, apoC-III, and significant reductions in atherogenic lipoproteins

Favorable safety and tolerability profile

BOSTON, MA and CARLSBAD, CA, USA I August 29, 2020 I Akcea Therapeutics, Inc. (NASDAQ: AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), presented data today from the Phase 2 study of AKCEA-APOCIII-LRx in an online Late Breaking Clinical Trial Session at the ESC Congress 2020, the annual meeting of the European Society of Cardiology.

Results showed that AKCEA-APOCIII-LRx met primary and key secondary endpoints with significant reductions in triglyceride (TG) and apoC-III levels, and a favorable safety and tolerability profile in the treatment of patients with hypertriglyceridemia who have established cardiovascular disease (CVD) or are at risk for CVD. 

"Hypertriglyceridemia and high levels of apoC-III are associated with increased residual risk for cardiovascular events, even in patients receiving appropriate lipid-lowering therapies. These results demonstrate that AKCEA-APOCIII-LRx can substantially reduce TG and apoC-III levels, and thus has the potential to fulfill an unmet need in this patient population," said Jean-Claude Tardif, M.D., director of the Research Center at the Montreal Heart Institute and professor of Medicine at University of Montreal.

AKCEA-APOCIII-LRx is designed using Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform to inhibit production of apolipoprotein C-III (apoC-III), a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Epidemiological studies show that apoC-III levels may help predict risk of CVD.

"We are encouraged by the results from our Phase 2 study, in which treatment with AKCEA-APOCIII-LRx significantly reduced triglycerides and other atherogenic lipoproteins in patients with hypertriglyceridemia and a history of CVD, or a high risk for CVD," said William Andrews, M.D., FACP, chief medical officer at Akcea. "We look forward to further assessing AKCEA-APOCIII-LRx in other severe diseases associated with high triglyceride levels, including familial chylomicronemia syndrome (FCS), for which we plan to initiate a Phase 3 trial later this year."

The Phase 2 study was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study designed to evaluate the safety, tolerability and efficacy of AKCEA-APOCIII-LRx in patients with hypertriglyceridemia and a clinical diagnosis of CVD or who are at high risk of CVD. The study was also designed to identify the optimal dose and dose regimen to lower TG, apoC-III and other lipid and lipoprotein levels for subsequent Phase 3 studies. The study involved 114 patients randomized to four cohorts and in a 4:1 ratio (treatment: placebo) within each cohort. AKCEA-APOCIII-LRx or placebo was administered via subcutaneous injection for at least six months, with some patients treated up to a year. Weekly, bi-weekly, and monthly dosing regimens were explored with total monthly doses ranging from 10 mg to 50 mg. Data from the Phase 2 study show:

  • Statistically significant dose-dependent reductions in fasting TGs compared to placebo at all dose levels with a 62% reduction at the highest dose (50 mg every four weeks), and with 91% of patients achieving TG levels of < 150 mg/dL (≤1.7 mmol/L) at this dose at six months
  • Significant reductions in apoC-III (up to 74%) and atherogenic lipoproteins including very low-density lipoprotein (VLDL) cholesterol (60%), non-high-density lipoprotein (non-HDL) cholesterol (24%), and apolipoprotein B, or apoB (16%)
  • High-density lipoprotein (HDL) cholesterol levels increased by up to 42%
  • AKCEA-APOCIII-LRx demonstrated a favorable tolerability and safety profile with mild treatment-emergent adverse events at the injection site being the most frequent

"These data further demonstrate the tremendous value that our LICA antisense platform brings to patients suffering from a broad range of diseases," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "We look forward to advancing AKCEA-APOCIII-LRx into Phase 3 development to address patient populations with high triglyceride levels".   

ABOUT AKCEA-APOCIII-LRx
AKCEA-APOCIII-LRx is an investigational antisense medicine 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 as well as elevated cardiovascular event risk. AKCEA-APOCIII-LRx was developed using Ionis' advanced LIgand Conjugated Antisense (LICA) technology platform. AKCEA-APOCIII-LRx will be entering Phase 3 development for patients with FCS, with plans to evaluate AKCEA-APOCIII-LRx in patients with other hypertriglyceridemia disorders. AKCEA-APOCIII-LRx was discovered by Ionis and has been co-developed by Akcea and Ionis.

ABOUT AKCEA THERAPEUTICS
Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), is a biopharmaceutical company focused on developing and commercializing medicines to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen), as well as advancing a mature pipeline of novel medicines, including AKCEA-APO(a)-LRx, vupanorsen (AKCEA-ANGPTL3-LRx), AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis' proprietary antisense technology. TEGSEDI is approved in the U.S., E.U., Canada and Brazil, and WAYLIVRA is approved in the E.U. Akcea is headquartered in Boston and is building the infrastructure to commercialize its medicines globally. Additional information about Akcea is available at www.akceatx.com and you can follow us on Twitter at @akceatx. 

ABOUT IONIS PHARMACEUTICALS, INC.
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, cardio-renal, metabolic, infectious, and pulmonary diseases. To learn more about Ionis visit www.ionispharma.com and follow us on Twitter @ionispharma.

SOURCE: Ionis Pharmaceuticals

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