CAMBRIDGE, Mass., Sept. 22, 2016 /PRNewswire/ -- Akcea
Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals,
Inc. (NASDAQ: IONS), today announced the publication in The
Lancet of key clinical results of two randomized, controlled
studies of IONIS-APO(a)Rx and
IONIS-APO(a)-LRx, the company's Lp(a)-lowering drugs
designed to treat cardiovascular disease and aortic valve
stenosis. Lipoprotein(a), or Lp(a), is an independent,
causal, genetic risk factor for cardiovascular disease and aortic
valve narrowing (stenosis). In these studies, substantial
Lp(a) reductions of up to 99% were noted, regardless of starting
Lp(a) levels. In addition, reductions in low-density
lipoprotein-cholesterol - (LDL-C) and pro-inflammatory oxidized
phospholipids were observed, as well as a decrease in the
inflammatory effects of white blood cells, which can initiate and
accelerate cardiovascular disease.
"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 Sotirios Tsimikas,
M.D., senior author of the paper, vice president of clinical
development at Ionis Pharmaceuticals and professor of medicine and
director of vascular medicine at the University of California, San Diego. "The
results from these studies show, for the first time, a new therapy
that can substantially reduce Lp(a), regardless of a patient's
starting Lp(a) level."
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 University of California San Diego School of
Medicine.
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
Richard Geary, Ph.D., senior vice
president of development at Ionis Pharmaceuticals.
"IONIS-APO(a)-LRx has the potential to eliminate nearly
all Lp(a)-mediated risk by normalizing Lp(a) levels in almost all
patients and reducing oxidized phospholipid levels and monocyte
inflammation. It has also demonstrated that it can reduce
LDL-cholesterol on top of current therapies. Furthermore,
Ionis' LICA technology shows unprecedented potency and tolerability
and represents the transformative potential for antisense drugs,
both in cardiovascular and in non-cardiovascular arenas."
ABOUT Lp(a)
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 the United
States are considered to be <30 mg/dL (<~75
nmol/L). The European Atherosclerosis Society suggests an
optimal Lp(a) level is <50 mg/dL (<125 nmol/L) levels.
Elevated Lp(a) is highly prevalent, with ~20% of the population
having levels >50 mg/dL and ~30% of the population having levels
>30 mg/dL. Lp(a) levels are not included in routine lipid
profile tests and frequently the risk of elevated Lp(a) goes
undetected until a cardiovascular event occurs. Additional
information is available through Lipoprotein(a) Foundation at
www.lipoproteinafoundation.org.
ABOUT IONIS-APO(a)-LRx
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 Pharmaceuticals, Inc., Akcea has a robust portfolio of
development-stage drugs covering multiple targets and disease
states. The drugs in Akcea's pipeline are designed using
Ionis' advanced RNA-targeted antisense technology to address a
number of lipid risk factors, including ApoC-III, triglycerides and
Lp(a). Akcea's most advanced program, volanesorsen, is in
Phase 3 development to treat patients with either familial
chylomicronemia syndrome (FCS) or familial partial lipodystrophy
(FPL), two orphan lipid disorders that are characterized by
extremely high triglycerides and ApoC-III. Akcea is located
in Cambridge, Massachusetts.
Additional information about Akcea is available at
www.akceatx.com.
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 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.
FORWARD-LOOKING STATEMENT
This press release includes forward-looking statements regarding
the business of Akcea Therapeutics, Inc., a wholly owned subsidiary
of Ionis Pharmaceuticals and the therapeutic and commercial
potential of Akcea's technologies and products in development,
including volanesorsen, and other products in development.
Any statement describing Akcea's 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 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 forward-looking statements
reflect the good faith judgment of its management, these statements
are based only on facts and factors currently known by Akcea.
As a result, you are cautioned not to rely on these forward-looking
statements. These and other risks concerning Akcea's programs
are described in additional detail in Akcea's parent company, Ionis
Pharmaceuticals, Inc.'s annual report on Form 10-K for the year
ended December 31, 2015, and its most
recent quarterly report on Form 10-Q, which are on file with the
SEC. Copies of these and other documents are available at
www.ionispharma.com.
In this press release, unless the context requires otherwise,
"Akcea," "Company," "we," "our," and "us" refers to Akcea
Therapeutics.
Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals,
Inc. Akcea Therapeutics™ is a trademark of Ionis
Pharmaceuticals, Inc. All rights reserved.
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SOURCE Ionis Pharmaceuticals, Inc.