CARLSBAD, Calif., and
CAMBRIDGE, Mass., Nov. 8, 2015 /PRNewswire/ -- Isis
Pharmaceuticals, Inc. (NASDAQ: ISIS), and its subsidiary, Akcea
Therapeutics, today announced positive results from a Phase 2 study
of ISIS-APO(a)Rx in which patients with high
lipoprotein(a), or Lp(a), achieved reductions in Lp(a) of up to 94
percent, with a mean reduction of 71 percent. Lp(a) is a
known driver of cardiovascular disease. They also announced
results from a Phase 1/2a study of ISIS-APO(a)-LRx in
which subjects with elevated Lp(a) achieved dose-dependent
reductions in Lp(a) of up to 99 percent.
ISIS-APO(a)-LRx is a LIgand Conjugated Antisense
(LICA) version of ISIS-APO(a)Rx.
ISIS-APO(a)-LRx demonstrated a greater than 30-fold
increase in potency in humans as compared to
ISIS-APO(a)Rx. Data from both the Phase 2 and
Phase 1/2a studies were presented today at the American Heart
Association Scientific Sessions by Joseph
Witztum, M.D., distinguished professor of medicine and
director of the atherosclerosis research group at the University of California, San Diego.
"Based on strong evidence, it is well accepted that elevated
levels of Lp(a) are a key driver of cardiovascular disease.
Because Lp(a) levels are largely unchanged throughout a person's
lifetime, high Lp(a) levels present at birth can result in
cumulative damage, which can be significant throughout the lifetime
of a patient. ISIS-APO(a)-LRx is the only drug in
clinical development that can specifically and robustly lower Lp(a)
in patients with elevated Lp(a)," said Sotirios Tsimikas, M.D., professor of medicine
and director of vascular medicine at the University of California, San Diego, and vice
president of clinical development at Isis Pharmaceuticals.
"In the studies presented today, patients achieved substantial
reductions in Lp(a) that were irrespective of their incoming Lp(a)
levels. These data support developing
ISIS-APO(a)-LRx for patients with high Lp(a), especially
patients with the highest Lp(a) levels, who are also at the
greatest risk."
Significant Reductions of Lp(a) in Phase 2 Study of
ISIS-APO(a)Rx
In the Phase 2 study, patients with
high or very high Lp(a) treated with ISIS-APO(a)Rx
achieved substantial reductions in Lp(a) of up to 94 percent with a
mean reduction of 71 percent (p ≤ 0.001). In this study, patients
treated with ISIS-APO(a)Rx achieved equal reductions of
Lp(a) regardless of incoming Lp(a) levels. The Phase 2 study was a
randomized, double-blind, placebo-controlled, dose-titration 12
week study evaluating ISIS-APO(a)Rx in 65 patients with
Lp(a) levels that were high (greater than or equal to 50 mg/dL and
less than 175 mg/dL) or very high (greater than or equal to 175
mg/dL). In this study, treatment with ISIS-APO(a)Rx was
generally well tolerated with no safety issues observed.
Significant, Sustained Lp(a) Reduction in Phase 1/2a Study of
ISIS-APO(a)-LRx
In the Phase 1/2a study, subjects
who received a single, low volume, subcutaneous injection of 10 mg,
20 mg, 40 mg or 80 mg of ISIS-APO(a)-LRx achieved
robust, dose-dependent and durable reductions of Lp(a).
Subjects who received a single dose of 80 mg
ISIS-APO(a)-LRx achieved substantial reductions in Lp(a)
of up to 97 percent and a mean reduction of 79 percent (p ≤ 0.01)
at 30 days. The long duration of effect resulted in
significant Lp(a) reductions of nearly 50 percent at 90 days after
the single dose.
Subjects who received multiple doses of 10 mg, 20 mg or 40 mg of
ISIS-APO(a)-LRx achieved dose-dependent, significant
reductions in Lp(a) of up to 99 percent, and a mean reduction of up
to 92 percent (p ≤0.001). In this study, subjects treated with
ISIS-APO(a)-LRx achieved similar reductions of Lp(a)
regardless of incoming Lp(a) levels. The safety and tolerability
profile of ISIS-APO(a)-LRx to date supports continued
development: out of 159 injections there were no injection
site reactions or flu-like symptoms reported.
"The enhanced potency of ISIS-APO(a)-LRx, the
opportunity for very infrequent dosing and the good safety and
tolerability profile significantly expands the patient populations
we plan to pursue for this drug. These data and our experience with
ISIS-APO(a)Rx support our plans to rapidly move forward
with the development of ISIS-APO(a)-LRx to treat
patients with a variety of Lp(a)-driven cardiovascular
diseases. We have a robust development program that addresses
near, mid and long-term commercial opportunities for
ISIS-APO(a)-LRx 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," said Paula Soteropoulos, president and chief
executive officer of Akcea Therapeutics. "Akcea is uniquely
positioned to maximize the therapeutic and commercial potential of
ISIS-APO(a)-LRx. We plan to rapidly advance this
new drug to market for patients with high Lp(a) who have no
effective treatment options today."
"ISIS-APO(a)-LRx is greater than 30-fold more potent
in humans than the unconjugated drug,
ISIS-APO(a)Rx. The significant increase in potency
and the longer half-life of the drug support the potential for
monthly, quarterly or even less frequent dosing. In addition,
ISIS-APO(a)-LRx demonstrates a good tolerability
profile. Given these data, we believe that the profile
conferred by our LICA technology significantly broadens the patient
populations we can target with our LICA drugs by supporting very
low volume, infrequent and well tolerated subcutaneous dosing,"
said Richard Geary, Ph.D., senior
vice president of clinical development at Isis
Pharmaceuticals. "We look forward to advancing
ISIS-APO(a)-LRx and the seven other LICA drugs we have
in our pipeline today and also adding new LICA drugs to our
pipeline in the coming years."
ISIS-APO(a)-LRx is a LICA antisense drug, which is
part of Isis' lipid franchise and is being developed and
commercialized by Akcea Therapeutics, Isis' wholly owned
subsidiary.
ABOUT Lp(a)
Lp(a) is considered a key driver for
cardiovascular disease due to its association with an increased
risk of coronary heart disease, atherosclerotic plaque formation
and calcific aortic valve stenosis. Lp(a) is a lipoprotein
particle that is assembled in the liver and consists of the
apolipoprotein(a) protein covalently linked to
LDL-cholesterol. Lp(a) levels in blood can vary greatly
between individuals due primarily to genetic variations in the gene
that encodes for apolipoprotein(a). As a result, Lp(a) levels
are genetically determined and remain constant throughout the life
of the individual. Diet and lifestyle changes have little
impact on Lp(a) levels and current therapies are not able to
adequately reduce elevated levels of Lp(a) to acceptable levels in
patients who have severely elevated Lp(a). As a general
guideline for ideal Lp(a) levels, the European Atherosclerosis
Society recommends that Lp(a) levels be less than or equal to 50
mg/dL. Additional information is available through Lipoprotein (a)
Foundation at www.lipoproteinafoundation.org.
Webcast
At 1:00 p.m. Eastern
Time, Nov. 8, 2015, Isis will
conduct a webcast to discuss the data presented today for
ISIS-APO(a)Rx and ISIS-APO(a)-LRx and review
the overall development plan for the Apo(a) program. A live
audio webcast of the presentation will be available on the
"Investor & Media" section of the Company's website,
www.isispharm.com. Interested parties may listen to the call
by dialing 877-443-5662. A replay will be available for a
limited time. The slides presented on the webcast will be
available on Isis' website at www.isispharm.com at the time of the
webcast and for a limited time after.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis 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, Isis 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 Isis
is developing and plans to commercialize through its wholly owned
subsidiary, Akcea Therapeutics, to treat patients with familial
chylomicronemia syndrome and familial partial lipodystrophy;
ISIS-TTRRx, a drug Isis is developing with GSK to treat
patients with all forms of TTR amyloidosis; and
ISIS-SMNRx, a drug Isis is developing with Biogen to
treat infants and children with spinal muscular atrophy.
Isis' patents provide strong and extensive protection for its drugs
and technology. Additional information about Isis is
available at www.isispharm.com.
ABOUT AKCEA THERAPEUTICS
Akcea Therapeutics is a
development and commercialization company focused on transforming
the lives of patients with serious cardiometabolic lipid disorders.
Established as a wholly-owned subsidiary of Isis Pharmaceuticals,
Inc., Akcea has a robust portfolio of development-stage drugs
covering multiple targets and disease states using advanced
RNA-targeted antisense therapeutics. Akcea's drug pipeline
includes novel antisense drugs designed to address a number of
lipid risk factors, including LDL-Cholesterol, apoC-III,
triglycerides and Lp(a). Akcea's most advanced program,
volanesorsen, is in Phase 3 development to treat patients with
ultra-orphan lipid disorders that are characterized by extremely
high triglycerides and ApoC-III, including familial chylomicronemia
syndrome (FCS) and familial partial lipodystrophy (FPL).
Akcea is located in Cambridge,
Massachusetts. Additional information about Akcea is
available at www.akceatx.com.
ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
This
press release includes forward-looking statements regarding Isis'
business, the business of Akcea Therapeutics, the therapeutic and
commercial potential of Isis' LICA technology, the discovery,
development, activity, therapeutic and commercial potential and
safety of ISIS-APO(a)Rx and ISIS-APO(a)-LRx
for the treatment of lipid disorders. 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, 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 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.
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SOURCE Isis Pharmaceuticals, Inc.