– Olezarsen
met the primary endpoint with statistically significant reduction
of fasting triglycerides and showed substantial, clinically
meaningful reduction in acute pancreatitis events –
– Results
demonstrate olezarsen may represent a novel treatment option for
this rare, life-threatening disease, for which there are no
approved treatments in the U.S. –
– Data
presented today at ACC 2024 and published in The New England
Journal of Medicine –
– Ionis to
host webcast on Monday, April 8 at
10:00 am ET –
CARLSBAD, Calif., April 7,
2024 /PRNewswire/ -- Ionis Pharmaceuticals,
Inc. (Nasdaq: IONS) today announced full results from the
Phase 3 Balance study of Ionis' lead independent investigational
medicine, olezarsen, for the treatment of adults with familial
chylomicronemia syndrome (FCS). The olezarsen 80 mg monthly dose
met the primary endpoint of significantly reducing triglycerides
(TGs) in patients with genetically validated FCS at six months. In
addition, olezarsen demonstrated robust and sustained
reductions in TGs and serum apolipoprotein C-III (apoC-III) levels.
Importantly, olezarsen reduced the incidence of acute pancreatitis
(AP) events over the 12-month treatment period compared to placebo.
Olezarsen also demonstrated a favorable safety and tolerability
profile. These results were presented in an oral presentation at
the 2024 American College of Cardiology (ACC) Annual Meeting in
Atlanta, Georgia and published
simultaneously in The New England Journal of Medicine
(NEJM). Based on these data, Ionis is pursuing regulatory
approval of olezarsen as a potential breakthrough treatment for
adults with FCS.
"As a physician who has seen first-hand the struggles of people
living with FCS and its serious complications, there is significant
need for an effective therapy to lower triglycerides and reduce
acute pancreatitis events," said Erik
Stroes, M.D., professor of medicine, Amsterdam University
Medical Centers, and a principal investigator of the Balance study.
"Olezarsen represents a potentially life-changing new medicine for
these patients who experience debilitating chronic symptoms,
including abdominal pain and cognitive symptoms, as well as
hospitalizations associated with potentially fatal acute
pancreatitis events."
Balance Study Results
In the study, patients were treated with olezarsen 80 mg (n=22),
50 mg (n=21) or placebo (n=23) once every four weeks.
- In the 80 mg group, olezarsen met the primary endpoint, with a
statistically significant placebo-adjusted reduction in TG levels
from baseline to six months (44%, p<0.001).
- Reductions from six to 12 months were sustained,
with olezarsen 80 mg achieving a placebo-adjusted 59%
reduction in TGs.
- ApoC-III placebo-adjusted reductions were robust and sustained
at six and 12 months (74% and 81% reductions, respectively).
- In the 50 mg group, olezarsen reduced TG levels, however this
difference was not statistically significant at six months compared
to placebo (22%, p=0.078).
- Reductions from six to 12 months were improved, with olezarsen
50 mg achieving a placebo-adjusted 44% reduction in TGs.
- Olezarsen-treated patients had markedly fewer AP events during
the 12-month period, compared to placebo.
- Eleven episodes of AP occurred in the placebo group versus one
episode in the 80 mg olezarsen group and one episode in the 50 mg
group.
- Furthermore, there was a substantially greater time to the
first event with olezarsen compared to placebo (one year (80 mg)
and 102 days (50 mg), vs. nine days for placebo).
- Olezarsen-treated patients experienced a placebo-adjusted 84%
reduction in all-cause hospitalizations between baseline and 12
months.
- A favorable safety and tolerability profile was observed, with
a higher number of treatment-emergent adverse events (TEAEs) in the
placebo group. There were no serious TEAEs related to olezarsen.
- The most common AEs were COVID-19, abdominal pain and diarrhea,
none of which were more frequent in patients treated with either
dose of olezarsen versus placebo.
- Serious AEs occurred in 14% of patients treated with olezarsen
80 mg, 19% treated with olezarsen 50 mg, and 39% treated with
placebo.
"Balance is the first clinical study to validate the association
of reduced triglyceride levels with reduced incidence of acute
pancreatitis events in patients with severely elevated
triglycerides. This important finding supports the potential for
olezarsen to be the standard of care for patients with FCS, if
approved. These data further strengthen our confidence for a
successful outcome in the ongoing Phase 3 CORE studies evaluating
olezarsen in the much more prevalent severe hypertriglyceridemia
patient population," said Brett P.
Monia, Ph.D., chief executive officer of Ionis. "Our team
looks forward to working closely with the FDA to advance the first
potential treatment for FCS in the U.S., and to successfully
delivering Ionis' first independent commercial launch later this
year, assuming priority review. We offer our sincerest gratitude to
the patients and investigators who participated in this pivotal
study."
The ACC Balance presentation can be found on Ionis' website
after today's presentation at 10:08 am
ET.
In addition to the Balance data, a late-breaking abstract
entitled, "Efficacy and Safety of Olezarsen in Patients with
Hypertriglyceridemia and High Cardiovascular Risk: Primary Results
of the Bridge-TIMI 73a Trial" was also presented at ACC and
published in NEJM.
Webcast
Ionis will host a webcast to discuss the detailed results from
the Balance study on Monday, April 8
at 10:00 am ET. Interested parties
may access the webcast here. A webcast replay will be available for
a limited time.
About the Balance Study
The global, multicenter, randomized, double-blind,
placebo-controlled Phase 3 Balance study (NCT04568434) enrolled 66
patients aged 18 and older with confirmed FCS. Patients in the
study received background therapies including statins, fibrates and
omega-3 fatty acids. Patients were randomized in a 1:1:1 ratio to
receive olezarsen 80 mg or 50 mg or placebo via subcutaneous
injection once every four weeks for 53 weeks. The primary endpoint
was the percent change from baseline in fasting triglyceride levels
at six months compared to placebo. Secondary endpoints included
percent changes in triglyceride levels at 12 months, percent
changes in other lipid parameters, and adjudicated acute
pancreatitis event rates over the treatment period.
About Olezarsen
Olezarsen is an RNA-targeted
investigational LIgand Conjugated Antisense
(LICA) medicine being evaluated for people at risk of disease due
to elevated triglyceride levels, including those with familial
chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit
the body's production of apoC-III, a protein produced in the liver
that regulates triglyceride metabolism in the blood.1,2
The U.S. FDA granted olezarsen Fast Track designation for the
treatment of FCS in January
2023, as well as Orphan Drug
designation and Breakthrough Therapy designation in
February 2024. In addition
to FCS, Ionis is evaluating olezarsen for the treatment of
severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials.
Olezarsen is an investigational medicine that has not been
reviewed or approved for the treatment of any disease by any
regulatory authority.
About FCS
FCS is a rare, genetic disease characterized by extremely
elevated triglyceride levels. It is caused by impaired function of
the enzyme lipoprotein lipase (LPL).3 Because of limited
LPL production or function, people with FCS cannot effectively
break down chylomicrons, lipoprotein particles that are 90%
triglycerides.3,4 FCS is estimated to impact one to 13
people per million in the U.S.5,6,7 People living with
FCS are at high risk of acute pancreatitis (AP) in addition to
other chronic health issues such as fatigue and severe, recurrent
abdominal pain.3,8,9 People living with FCS are
sometimes unable to work, adding to the burden of
disease.9
Currently, there are no U.S. FDA-approved therapies for the
treatment of FCS and standard triglyceride lowering therapies are
generally ineffective in patients with FCS.10,11 People
living with this condition currently rely solely on nutrition
management through extremely restrictive and difficult to manage
diets to navigate the health risks associated with
FCS.11,12
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring
better futures to people with serious diseases. Ionis currently has
five marketed medicines and a leading pipeline in neurology,
cardiology, and other areas of high patient need. As the pioneer in
RNA-targeted medicines, Ionis continues to drive innovation in RNA
therapies in addition to advancing new approaches in gene editing.
A deep understanding of disease biology and industry-leading
technology propels our work, coupled with a passion and urgency to
deliver life-changing advances for patients. To learn more about
Ionis, visit Ionispharma.com and follow us on X (Twitter)
and LinkedIn.
Forward-looking Statements
This press release includes forward-looking statements regarding
olezarsen, Ionis' business, and the therapeutic and commercial
potential of Ionis' commercial medicines, additional medicines in
development and technologies. 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 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. Except as required by
law, we undertake no obligation to update any forward-looking
statements for any reason. 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, 2023, and most recent Form 10-Q, which
are on file with the SEC. Copies of these and other documents are
available at www.ionispharma.com.
Ionis Pharmaceuticals® is a registered trademark of Ionis
Pharmaceuticals, Inc.
Ionis Pharmaceuticals Investor Contact: D. Wade Walke, Ph.D. - info@ionisph.com -
760-603-2331; Ionis Pharmaceuticals Media Contact: Hayley Soffer -
CorporateCommunications@ionisph.com - 760-603-4679
1Alexander VJ, et al. Eur Heart J
2019;40(33):2785-2796.
2Tardif JC, et al. Eur Heart J
2022;43(14):1401-1412.
3Gaudet D, et al. N Engl J Med. 2014;371:2200-2206.
4Ginsberg HN, et al. Eur Heart
J. 2021;42:4791-4806.
5Pallazola VA, et al. Eur J Prev Cardiol
2020;27(19):2276-8.
6Warden BA, et al. J Clin Lipidol 2020;14(2):201-6.
7Tripathi M, et al. Endocr Pract 2021;27(1):71-6.
8Bashir B, et al. Metabolites. 2023;(5):621.
9Davidson M, et al. J Clin Lipidol.
2018;12(4):898-907.e2.
10Gouni-Berthold I. J Endocr Soc. 2019;4(2):bvz035.
11Paquette M, et al. Atherosclerosis.
2019;283:137-142.
12Williams L, et al. J Clin Lipidol. 2018;4:908-919.
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SOURCE Ionis Pharmaceuticals, Inc.