- ETESIAN Phase 2b
study of ION449 (AZD8233) met its primary and secondary endpoints;
ION449 was generally well tolerated
- ION449 demonstrated potential best-in-class efficacy
profile for a self-administered subcutaneous monthly dose
regimen
- Study findings warrant further clinical development
of ION449 for patients with hypercholesterolemia at high
cardiovascular risk
CARLSBAD, Calif., April 4,
2022 /PRNewswire/ -- Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS), the leader in antisense therapeutics, and its
partner, AstraZeneca, today announced positive data from the
ETESIAN Phase 2b study of ION449
(AZD8233), an investigational antisense medicine designed to reduce
blood cholesterol levels in patients with hypercholesterolemia by
targeting proprotein convertase subtilisin/kexin type 9 (PCSK9).
These data were presented at the American College of Cardiology's
71st Annual Scientific Session & Expo.
The ETESIAN Phase 2b study's
objective was to assess the efficacy, safety and tolerability of
ION449 in patients with high-risk hypercholesterolemia. The study
met its primary endpoint in reducing serum LDL-C levels by up to
79%. Both the 50mg and 90mg doses reached statistically significant
and clinically meaningful reductions in LDL-C levels from baseline
of 73% (95% confidence interval [CI]: 77%, 68%) and 79% (95%
CI: 83%, 76%), respectively, versus 2% (95% CI: 17%, -15%) for
placebo. The reductions in LDL-C were maintained until week 14 (6
weeks after the last dose).
The trial also met the secondary endpoints, including
significantly reducing PCSK9 levels by up to 94%. The 50mg and
90mg doses achieved reductions in PCSK9 levels of 89% (95% CI: 91%,
86%) and 94% (95% CI: 95%, 92%), respectively, versus 5% (95% CI:
23%, -18%) for placebo. The sustained reductions in PCSK9
levels were maintained until week 14 (6 weeks after last dose).
Reducing PCSK9 levels leads to lower LDL-C levels in the
bloodstream, which is known to reduce the risk of developing
coronary heart disease.
ION449 was generally well tolerated during the 12-week treatment
period and the 12-week follow up period in the study.
"The positive results of the ETESIAN study, along with the
clinical studies to date, reinforces our confidence that ION449
(AZD8233) is a potential new treatment option that may be able to
change the current standard of care for patients affected by
hypercholesterolemia who have cardiovascular disease," said
Brett P. Monia, Ph.D., Ionis' chief
executive officer.
"Today, we are pleased to announce that ETESIAN Phase
2b for ION449 (AZD8233) demonstrated
a clear dose-response for both PCSK9 and LDL-C levels. The results
underscore ION449's (AZD8233) potential best-in-class efficacy
profile and support further development of ION449 (AZD8233) as a
next-generation PCSK9 inhibitor that is self-administered monthly,"
said Mene Pangalos, executive vice
president and president, BioPharmaceuticals R&D at
AstraZeneca.
ION449 is being developed by AstraZeneca as part of a
collaboration between Ionis and AstraZeneca.
About ION449
ION449 (AZD8233) dosed once monthly via subcutaneous
administration, is an investigational medicine that uses Ionis'
advanced LIgand-Conjugated Antisense (LICA)
technology platform. It is designed to reduce plasma levels of
proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is
integrally involved in the regulation of LDL-cholesterol. Genetic
studies have shown that individuals with life-long reduction of
LDL-C due to reduced function of PCSK9 have substantially reduced
risk of cardiovascular disease. Pharmacological inhibition of PCSK9
substantially lowers LDL-C. ION449 is designed to reduce the liver
production of PCSK9 and lower the plasma level of LDL-C and thus
reduce the risk of cardiovascular disease.
Elevated levels of LDL-C are a key risk factor in the
development of cardiovascular disease, including heart attack,
stroke and peripheral arterial disease. Higher levels of LDL-C in
the blood are directly related to greater risk of vascular disease,
while reduction of LDL-C leads to a significant decrease in risk.
Despite the presence of several lipid-lowering agents, many
patients are unable to achieve recommended LDL-C levels and remain
at increased risk for cardiovascular disease. The development of
additional, highly potent LDL-C lowering drugs can address this
persistent unmet need.
About ETESIAN
ETESIAN is a randomized, double-blind, placebo-controlled,
dose-ranging Phase 2b study in
patients with hypercholesterolemia. The primary objective was to
assess the effect of different doses of ION449 (AZD8233) on LDL-C
compared to placebo at Week 12 in patients on statin therapy.
Secondary endpoints included change in PCSK9 levels and the
assessment of safety and tolerability of ION449.
The study had 119 participants, aged 18-75, who had LDL-C levels
between 70 and 190mg/dL and were receiving moderate or
high-intensity statin therapy.
Three dose levels of ION449 were evaluated (15mg, 50mg, 90mg),
given monthly by sub-cutaneous injection over the 12-week dosing
period. All active arms demonstrated reductions in LDL-C and PCSK9
levels at week 12 compared to placebo.
The percent changes from baseline to week 12 in LDL-C at the
15mg, 50mg and 90mg monthly dose were –39% (95% confidence interval
[CI] –48%, –29%), –73% (95% CI: –77%, –68%), –79% (95% CI: –83%,
–76%), respectively. The percent changes from baseline to week 12
in PCSK9 levels at the 15mg, 50mg and 90mg monthly dose were –58%
(95% CI, –66%, –48%), –89% (95% CI: –91%, –86%), –94% (95% CI:
–95%, –92%), respectively. ION449 was generally well-tolerated. The
adverse events (AEs) were similar between the 15mg, 50mg and
placebo groups. Most AEs were mild to moderate including transient,
moderate treatment-emergent elevations in liver enzyme levels in
the 90mg group.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been the leader in
RNA-targeted therapy, pioneering new markets and changing standards
of care with its novel antisense technology. Ionis currently has
three marketed medicines and a premier late-stage pipeline
highlighted by industry-leading neurological and cardiometabolic
franchises. Our scientific innovation began and continues with the
knowledge that sick people depend on us, which fuels our vision of
becoming a leading, fully integrated biotechnology company.
To learn more about Ionis, visit www.ionispharma.com and follow
us on Twitter @ionispharma.
Ionis' Forward-looking Statements
This press release includes forward-looking statements regarding
Ionis' business and the therapeutic and commercial potential of
Ionis' technologies, ION449 and other products in development. Any
statement describing Ionis' 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, including those related
to the impact COVID-19 could have on our business, and including
but not limited to, those related to our commercial products and
the medicines in our pipeline, and particularly those inherent in
the process of discovering, developing and commercializing
medicines that are safe and effective for use as human
therapeutics, and in the endeavor of building a business around
such medicines. 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 Ionis' forward-looking statements reflect the good
faith judgment of its management, these statements are based only
on facts and factors currently known by Ionis. As a result, you are
cautioned not to rely on these forward-looking statements. These
and other risks concerning Ionis' programs are described in
additional detail in Ionis' annual report on Form 10-K for the year
ended Dec. 31, 2021, which is 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,
"Ionis," "Company," "we," "our," and "us" refers to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals,
Inc.
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SOURCE Ionis Pharmaceuticals, Inc.