Approximately 98% of patients receiving highest
dose achieved reductions in Lp(a) levels below the established
threshold of risk for CVD events
Akcea Therapeutics, Inc. (NASDAQ: AKCA), an affiliate of Ionis
Pharmaceuticals, Inc., and Ionis Pharmaceuticals,
Inc. (NASDAQ: IONS), today announced that data from the Phase
2 clinical study of AKCEA-APO(a)-LRx in patients with established
cardiovascular disease (CVD) and elevated levels of lipoprotein(a),
or Lp(a), were presented in a late-breaking clinical trial
presentation at the American Heart Association Scientific Sessions
in Chicago November 10, 2018.
Elevated Lp(a) is an independent, hereditary risk factor for CVD
that cannot be well controlled with lifestyle modifications such as
diet or exercise or with treatment using existing
cholesterol-lowering therapies. It is estimated that there are 8 to
10 million treatable patients living with cardiovascular disease
and elevated levels of Lp(a).
“Lp(a) is a hereditary cardiovascular disease risk factor that
impacts millions of families and cannot be addressed by diet and
exercise. A drug that reduces Lp(a) could be a paradigm shift for
the cardiovascular community. Physicians are looking for a tool to
treat their patients who today have no pharmacological option to
sustainably reduce their Lp(a) levels below 50mg/dL, the threshold
for a Lp(a)-driven cardiac event such as a heart attack or stroke,”
said Dr. Sotirios Tsimikas, vice president of global
cardiovascular development at Ionis Pharmaceuticals and professor
of medicine and director of vascular medicine at the University of
California San Diego and an international expert on Lp(a). “The
data from this study represent an important step forward. These
results demonstrate that AKCEA-APO(a)-LRx can greatly lower Lp(a)
levels with a favorable safety and tolerability profile. These
results warrant advancement of this program to Phase 3 and I look
forward to participating in its future development.”
Patients were treated with AKCEA-APO(a)-LRx or placebo for at
least six months, with some patients treated up to one year. The
study met all primary and secondary efficacy endpoints analyzed at
6 months. Results from the study show statistically significant and
dose dependent reductions from baseline in Lp(a) levels:
Lp(a) |
Pooled placebo(n=47) |
20 mg every 4 weeks(n=48) |
40 mg every 4 weeks(n=48) |
20 mg every 2 weeks(n=48) |
60 mg every 4 weeks(n=47) |
20 mg weekly(n=48) |
LSMean % change in Lp(a) |
-6 |
-35P=0.0032 |
-56P<0.0001 |
-58P<0.0001 |
-72P<0.0001 |
-80P<0.0001 |
*LSMean: Least squares mean
- Approximately 98% of patients in the 20mg weekly cohort and
approximately 81% of patients in the 60mg every 4 week cohort
achieved clinically significant reductions in Lp(a) levels bringing
them below the recommended threshold of risk for CVD events (<50
mg/dL).
- Treatment with AKCEA-APO(a)-LRx was associated with decreases
in LDL-C, apoB, OxPL-apoB, OxPL-apo(a).
- Most adverse events were mild. The most frequent adverse
events were injection site reactions (ISRs). ISRs occurred in 26%
of patients and were mostly mild and one patient discontinued due
to an ISR.
- There were no safety concerns related to platelet counts, liver
function or renal function.
- No patient in the study experienced a confirmed platelet count
below 100,000/mm3. The incidence of platelet levels below normal
(140,000/mm3) was comparable between the active (10.5%) and placebo
(14.9%) groups.
- Approximately 90% of patients completed treatment and the rate
of discontinuation was comparable between the active (12.1%) and
placebo (14.9%) groups.
“These data show that AKCEA-APO(a)-LRx significantly reduces
Lp(a) in patients with pre-existing cardiovascular disease due to
elevated Lp(a) levels. AKCEA-APO(a)-LRx is the first and only drug
to show a clinically significant reduction of Lp(a) levels and a
favorable safety and tolerability profile in patients with this
genetic condition,” said Dr. Louis O’Dea, chief medical officer at
Akcea Therapeutics. “This is a particularly important advancement
as elevated Lp(a) can cause cardiac events for patients as early as
in their 30s and 40s. We are actively working with Novartis to
prepare for an end of Phase 2 meeting with FDA. We look forward to
advancing this important development program into Phase 3.”
AKCEA-APO(a)-LRx is an antisense drug developed using
Ionis’ proprietary LICA technology, which has potential to produce
new drugs that can be used at lower doses and with less frequent
administration than non-LICA antisense drugs. Results from separate
Phase 1 studies of eight LICA drugs in development, including three
at Akcea, have shown that doses up to 30-fold lower than non-LICA
drugs can result in consistent target reductions with a favorable
safety and tolerability profile.
“The AKCEA-APO(a)-LRx Phase 2 study is the largest and
longest study to evaluate the Ionis LICA technology platform to
date. We are encouraged by the robust reductions in Lp(a) levels
and the favorable safety and tolerability profile,” said Brett
Monia, Ph.D., chief operating officer at Ionis. “Because Lp(a)
cannot be easily targeted with small molecules or antibodies,
inhibition of apolipoprotein(a) is a great example of how antisense
technology can have an impact where no other therapeutic approaches
have proven effective. We look forward to further assessing our
LICA platform with the 13 programs now in development.”
Development of AKCEA-APO(a)-LRx is part of a strategic
collaboration between Akcea and Novartis. If Novartis
exercises its option to license AKCEA-APO(a)-LRx after an end
of Phase 2 meeting with the FDA, Akcea will receive a $150 million
milestone payment of which 50% will be paid to Ionis. After
exercise of its option, Novartis will be responsible for all future
development activities for AKCEA-APO(a)-LRx including a planned
global Phase 3 cardiovascular outcomes study and, pending
regulatory approval, global commercialization activities. As part
of the collaboration, Akcea has the rights to co-commercialize
AKCEA-APO(a)-LRx in selected markets, on mutually agreed terms and
conditions.
ABOUT AKCEA-APO(a)-LRx AND THE PHASE 2
STUDYAKCEA-APO(a)-LRx is an antisense drug that uses
Ionis’
advanced LIgand Conjugated Antisense,
or LICA technology. AKCEA-APO(a)-LRx inhibits the production
of apolipoprotein(a), or Apo(a), protein, thereby reducing
Lp(a).
The Phase 2 study was designed to evaluate the safety and
tolerability of AKCEA-APO(a)-LRx and to determine the appropriate
dosing for a planned Phase 3 cardiovascular outcomes study.
The randomized, double-blind, placebo-controlled, dose-ranging
Phase 2 study included 286 patients with established CVD and high
Lp(a) levels (baseline mean of approximately 100mg/dL [250 nmol/L]-
more than three times the upper limit of normal). The trial had
five cohorts: 20 mg (every 4 weeks), 40 mg (every 4 weeks), 60
(every 4 weeks), 20 mg (every 2 weeks), and 20 mg (every week). The
primary efficacy endpoint was the percent change in Lp(a) from
baseline at the primary analysis time point (6 months) compared to
placebo. The secondary efficacy endpoints were mean percent change
in LDL-C, apoB, OxPL-apoB, OxPL-apo(a), and the number of patients
reaching pre-specific thresholds of <125 nmol/L (<50 mg/dL)
or <75 nmol/L (<30 mg/dL). All patients were treated for at
least six months, with some patients treated up to one year.
ABOUT
Lp(a)
Lipoprotein(a), or Lp(a) is made up of apo(a) protein bound to LDL
cholesterol and contains oxidized phospholipids, resulting in an
atherogenic, pro-inflammatory and thrombogenic lipoprotein.
Elevated Lp(a) is recognized as an independent, genetic cause of
cardiovascular disease present in approximately 20-30% of the
population. Lp(a) levels are determined at birth and, therefore,
lifestyle modifications, including diet and exercise, do not impact
Lp(a) levels.
For additional information about Lp(a), please see the
Lipoprotein(a) Foundation at
http://www.lipoproteinafoundation.org/.
About Akcea
Therapeutics,
Inc. Akcea Therapeutics, Inc., an
affiliate of Ionis Pharmaceuticals, Inc., is a
biopharmaceutical company focused on developing and commercializing
drugs to treat patients with serious and rare diseases. Akcea is
advancing a mature pipeline of six novel drugs, including
TEGSEDI™ (inotersen), WAYLIVRA™ (volanesorsen),
AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx, AKCEA-APOCIII-LRx, and
AKCEA-TTR-LRx, all with the potential to treat multiple diseases.
All six drugs were discovered by and are being co-developed with
Ionis, a leader in antisense therapeutics, and are based on Ionis’
proprietary antisense technology. TEGSEDI is approved in the U.S.,
E.U. and Canada. WAYLIVRA is under regulatory review for the
treatment of familial chylomicronemia syndrome, or FCS, and is
currently in Phase 3 clinical development for the treatment of
people with familial partial lipodystrophy, or FPL. Akcea is
building the infrastructure to commercialize its drugs globally.
Akcea is a global company headquartered in Boston, Massachusetts.
Additional information about Akcea is available
at www.akceatx.com.
About Ionis Pharmaceuticals As the leader in
RNA-targeted drug discovery and development, Ionis has created an
efficient, broadly applicable, proprietary antisense technology
platform with the potential to 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 – such as children and
adults with spinal muscular atrophy (SMA). We created
SPINRAZA® (nusinersen)* and are proud to have brought new hope
to the SMA community by developing the first and only approved
treatment for this disease.
Our sights are set on all the patients we have yet to reach with
a pipeline of more than 40 drugs with the potential to treat
patients with cardiovascular disease, rare diseases, neurological
diseases, infectious diseases and cancer. We created TEGSEDI™
(inotersen) the world’s first RNA-targeted therapeutic approved for
the treatment of polyneuropathy in adult patients with hereditary
transthyretin (TTR) amyloidosis (ATTR) that our affiliate Akcea
Therapeutics is commercializing. Together with Akcea, we are
also bringing new medicines to patients with cardiometabolic lipid
disorders.
To learn more about Ionis follow us on twitter @ionispharma or
visit http://ir.ionispharma.com/.
*Spinraza is marketed by Biogen.
AKCEA AND IONIS
FORWARD-LOOKING
STATEMENT This press release includes
forward-looking statements regarding the business of Akcea
Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. and the
therapeutic and commercial potential of AKCEA-APO(a)-LRx. Any
statement describing Akcea’s or Ionis’ goals, expectations,
financial or other projections, intentions or beliefs, including
the commercial potential of AKCEA-APO(a)-LRx or other of Akcea’s or
Ionis’ drugs in development 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 and Ionis’ 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 and Ionis’ forward-looking statements reflect the good
faith judgment of its management, these statements are based only
on facts and factors currently known by Akcea and Ionis. As a
result, you are cautioned not to rely on these forward-looking
statements. These and other risks concerning Ionis’ and Akcea’s
programs are described in additional detail in Ionis’ and Akcea’s
quarterly reports on Form 10-Q and annual reports on Form 10-K,
which are on file with the SEC. Copies of these and other documents
are available from each company.
In this press release, unless the context requires otherwise,
“Ionis”, “Akcea,” “Company,” “Companies” “we,” “our,” and “us”
refers to Ionis Pharmaceuticals and/or Akcea Therapeutics.
Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals,
Inc. Akcea Therapeutics™, TEGSEDI™ and WAYLIVRA™ are
trademarks of Akcea Therapeutics, Inc.For
More
Information:
Akcea Investor Contact:Kathleen GallagherVice
President of Communications and Investor Relations
(617)-207-8509kgallagher@akceatx.com
Akcea Media Contact:Bill BerryBerry &
CompanyT: 212 253-8881bberry@berrypr.com
Lynn GranitoBerry & CompanyT: 212
253-8881lgranito@berrypr.com
Ionis Investor Contact:D. Wade Walke, Ph.D.Vice
President, Investor Relations760-603-2741wwalke@ionisph.com
Ionis Media Contact:Roslyn PattersonVice
President, Corporate
Communications760-603-2681rpatterson@ionisph.com
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