"Patients with Lp(a)-driven cardiovascular disease have no viable therapeutic options today for significantly lowering their Lp(a) to a level where risk can be minimal. And, since a patient's Lp(a) level is genetically determined, changes in lifestyle, such as diet and exercise, have minimal, if any, impact," said
The paper titled "Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials" (Viney et al., The Lancet) documents the results of two clinical studies testing the safety, tolerability and efficacy of antisense drugs designed to lower elevated Lp(a) levels. The published clinical findings are a result of a partnership with the Sulpizio Cardiovascular Center at the
The IONIS-APO(a)Rx study is the first randomized clinical study to evaluate a specific Lp(a)-lowering therapy in patients with or at high risk for cardiovascular disease with elevated Lp(a) levels. Treatment with IONIS-APO(a)Rx in patients with high (50-175 mg/dL or 125-437 nmol/L) or very high (>175 mg/dL or >437 nmol/L) Lp(a) levels resulted in a mean reduction in Lp(a) of 67-72%, with up to a 94% reduction. In addition, a significant reduction was noted in pro-inflammatory oxidized phospholipids and the inflammatory effects of monocytes, as well LDL-C.
The IONIS-APO(a)-LRx trial studied an optimized and more potent LICA drug that contains a GalNAc moiety that enhances delivery of drug to hepatocytes where Lp(a) is made and assembled. In this first-in-man study, multiple doses of IONIS-APO(a)-LRx resulted in mean reductions in Lp(a) of 66% in the 10 mg group, 80% in the 20 mg group, and 92% in the 40 mg group, and up to a 99% reduction. In these short-term studies, the drug was well tolerated. No side effects were noted in any laboratory tests and there were no injection site reactions.
"IONIS-APO(a)-LRx has shown more than 30-fold greater potency compared to IONIS-APO(a)Rx. This means that with much lower doses of IONIS-APO(a)-LRx we can achieve similar or better efficacy than IONIS-APO(a)Rx and monthly or even less frequent dosing may be feasible," said
Lipoprotein (a), or Lp(a), is an independent, causal, genetic risk factor for cardiovascular disease, including myocardial infarction, stroke, peripheral arterial disease and calcific aortic valve stenosis. Lp(a) is a lipoprotein particle that is synthesized and assembled in the liver and consists of one apolipoprotein(a) protein covalently linked to one LDL particle. Elevated Lp(a) levels in blood are primarily due to genetic variations in the LPA gene that encodes for apolipoprotein(a) and cannot be lowered by diet, exercise or other lipid-lowering therapies, such as statins. In fact, statins may raise Lp(a) levels. Normal Lp(a) levels in
IONIS-APO(a)-LRx is a LIgand Conjugated Antisense (LICA) drug designed to reduce apolipoprotein(a) in the liver to offer a direct approach for reducing plasma levels of lipoprotein(a), or Lp(a). IONIS-APO(a)-LRx is in development to treat patients with high Lp(a) levels. Akcea has the first and only clinical program to selectively and robustly reduce Lp(a) in patients by inhibiting apo(a) and plans to develop IONIS-APO(a)-LRx with a robust program that addresses near, mid and long-term commercial opportunities by focusing initially on patients who have the greatest need and, in the long-term, on patients with more generalized Lp(a)-driven cardiovascular risk.
ABOUT AKCEA THERAPEUTICS
Akcea Therapeutics is focused on developing and commercializing drugs for patients with serious cardiometabolic diseases caused by lipid disorders. Established as a wholly owned subsidiary of
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 a dozen drugs in mid- to late-stage development. Drugs currently in Phase 3 development include volanesorsen, a drug Ionis is developing and plans to commercialize through its wholly owned subsidiary, Akcea Therapeutics, to treat patients with either familial chylomicronemia syndrome or familial partial lipodystrophy; IONIS-TTRRx, a drug Ionis is developing with GSK to treat patients with all forms of TTR amyloidosis; and nusinersen, a drug Ionis is developing with Biogen to treat infants and children with spinal muscular atrophy. Ionis' patents provide strong and extensive protection for its drugs and technology. Additional information about Ionis is available at www.ionispharma.com.
This press release includes forward-looking statements regarding the business of
In this press release, unless the context requires otherwise, "Akcea," "Company," "we," "our," and "us" refers to Akcea Therapeutics.
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D. Wade Walke, Ph.D., Vice President, Corporate Communications and Investor Relations, 760-603-2741