CARLSBAD, Calif., March 23, 2015 /PRNewswire/ -- Isis
Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today positive
results from a Phase 1 study with ISIS-ANGPTL3Rx.
In this study, healthy volunteers treated with
ISIS-ANGPTL3Rx achieved dose-dependent, statistically
significant reductions in angiopoietin-like 3 (ANGPTL3) of up to 93
percent with a mean reduction of up to 84 percent from baseline
(p<0.001). In addition, statistically significant
reductions from baseline in lipid parameters were observed,
including up to 63% with a mean reduction of up to 49% (p<0.01)
in triglycerides and up to 46% with a mean reduction of up to 28%
(p<0.001) in total cholesterol. ANGPTL3 is a protein that
acts as a key regulator of these blood lipids. These data were
presented at the 83rd European Atherosclerosis Society
in Glasgow, United
Kingdom.
"We are encouraged with the performance of
ISIS-ANGPTL3Rx in healthy volunteers. Based on
data from preclinical models of hyperlipidemia, we expect to see
even greater lipid reductions in patients with hyperlipidemia than
in healthy volunteers," said Richard
Geary, senior vice president at Isis Pharmaceuticals. "In
fact, in this study we observed that healthy volunteers with higher
baseline lipid levels experienced larger lipid reductions than
those with lower baseline lipid levels."
"ANGPTL3 is a very interesting target for the management of both
plasma triglycerides and cholesterol at the same time. We know from
genetic studies of patients who are heterozygous for
loss-of-function mutations in their ANGPTL3 gene that they have
half-normal levels of plasma ANGPTL3, and correspondingly, lower
levels of plasma triglycerides and cholesterol. Patients who are
homozygous for such loss-of-function mutations have exceedingly low
plasma levels of triglycerides and cholesterol, which are both risk
factors for cardiovascular disease. In contrast, humans
with different mutations in ANGPTL3 that raise plasma ANGPTL3
levels have increased lipid levels. In addition, pre-clinical
studies in animal models demonstrate that raising plasma ANGPTL3
levels increase, and lowering plasma ANGPTL3 levels decrease
triglyceride and cholesterol levels," said Joseph L. Witztum, M.D., professor of medicine
at the University of California, San
Diego. "All of these data strongly support the idea
that lowering plasma ANGPTL3 in humans is a potentially important
strategy to reduce multiple cardiovascular risk factors."
"ISIS-ANGPTL3Rx is one of the drugs in our lipid
franchise that our wholly owned subsidiary, Akcea Therapeutics, is
developing and plans to commercialize. The team at Akcea has
already begun to outline the development and commercialization
plans for ISIS-ANGPTL3Rx, together with the other drugs
in our lipid franchise, to provide the best opportunity for each
drug to succeed and bring the highest possible value to those
patients who need these therapies the most," said Lynne Parshall, chief operating officer at
Isis.
The Phase 1 study of ISIS-ANGPTL3Rx was a blinded,
placebo-controlled, dose-escalation study in healthy
volunteers. The study was designed to assess the safety,
tolerability and pharmacokinetics of ISIS-ANGPTL3Rx.
ISIS-ANGPTL3Rx was evaluated in single and
multiple doses ranging from 50 mg per week up to 400 mg per week
for the single dose and 100 mg per week up to 400 mg per week for
the multiple dose. In this study, ISIS-ANGPTL3Rx
was generally well tolerated.
ISIS-ANGPTL3Rx is an antisense drug designed to
reduce ANGPTL3. ANGPTL3 is produced in the liver and
regulates lipid, glucose and energy metabolism. In
preclinical studies, antisense inhibition of ANGPTL3 resulted in
robust reductions of multiple lipid parameters, including
total-cholesterol, and triglycerides.
ISIS-ANGPTL3Rx is part of Isis' lipid franchise and, as
such, Akcea Therapeutics, Isis' wholly owned subsidiary, is
responsible for developing ISIS-ANGPTL3Rx.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting
its leadership position in RNA-targeted technology to discover and
develop novel drugs for its product pipeline and for its
partners. Isis' broad pipeline consists of 38 drugs to treat
a wide variety of diseases with an emphasis on cardiovascular,
metabolic, severe and rare diseases, including neurological
disorders, and cancer. Isis' partner, Genzyme, is
commercializing Isis' lead product, KYNAMRO®, in
the United States and other
countries for the treatment of patients with homozygous FH.
Isis has numerous drugs in Phase 3 development in severe/rare
diseases and cardiovascular diseases. These include
ISIS-APOCIIIRx, a drug Isis is developing and plans to
commercialize through its wholly owned subsidiary, Akcea
Therapeutics, to treat patients with familial chylomicronemia
syndrome and partial lipodystrophy; ISIS-TTRRx, a drug
Isis is developing with GSK to treat patients with the
polyneuropathy and cardiomyopathy forms of TTR amyloidosis; and
ISIS-SMNRx, a drug Isis is developing with Biogen Idec
to treat infants and children with spinal muscular atrophy, a
severe and rare neuromuscular disease. Isis' patents provide
strong and extensive protection for its drugs and technology.
Additional information about Isis is available at
www.isispharm.com.
ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
This
press release includes forward-looking statements regarding the
development, activity, therapeutic potential and safety of
ISIS-ANGPTL3Rx and the discovery, development and
therapeutic potential of an antisense drug for the treatment of
patients with elevated LDL-cholesterol. Any statement
describing Isis' 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. Isis' 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 Isis' forward-looking statements reflect the good faith
judgment of its management, these statements are based only on
facts and factors currently known by Isis. As a result, you
are cautioned not to rely on these forward-looking
statements. These and other risks concerning Isis' programs
are described in additional detail in Isis' annual report on Form
10-K for the year ended December 31,
2014, which is on file with the SEC. Copies of this
and other documents are available from the Company.
In this press release, unless the context requires otherwise,
"Isis," "Company," "we," "our," and "us" refers to Isis
Pharmaceuticals and its subsidiaries.
Isis Pharmaceuticals® is a registered trademark of
Isis Pharmaceuticals, Inc. Akcea Therapeutics™ is a trademark
of Isis Pharmaceuticals, Inc. KYNAMRO® is a
registered trademark of Genzyme Corporation.
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SOURCE Isis Pharmaceuticals, Inc.