Approximately 98% of patients receiving highest dose achieved reductions in Lp(a) levels below the
established threshold of risk for CVD events
Favorable safety and tolerability profile observed in largest study ever conducted in patients with
cardiovascular disease and elevated Lp(a)
BOSTON and CARLSBAD, Calif., Nov. 12, 2018 (GLOBE NEWSWIRE) -- 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
|
-35
P=0.0032
|
-56
P<0.0001
|
-58
P<0.0001
|
-72
P<0.0001
|
-80
P<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 STUDY
AKCEA-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 Gallagher
Vice President of Communications and Investor Relations
(617)-207-8509
kgallagher@akceatx.com
Akcea Media Contact:
Bill Berry
Berry & Company
T: 212 253-8881
bberry@berrypr.com
Lynn Granito
Berry & Company
T: 212 253-8881
lgranito@berrypr.com
Ionis Investor Contact:
D. Wade Walke, Ph.D.
Vice President, Investor Relations
760-603-2741
wwalke@ionisph.com
Ionis Media Contact:
Roslyn Patterson
Vice President, Corporate Communications
760-603-2681
rpatterson@ionisph.com