- Olezarsen met the primary endpoint with a statistically
significant reduction in triglyceride levels versus
placebo
- First study to show an absolute reduction in
acute pancreatitis in FCS patients, with olezarsen 80 mg
monthly dose reducing events by 100 percent
- Olezarsen demonstrated a favorable safety and tolerability
profile
- Ionis plans to file a New Drug Application with U.S. FDA in
preparation for first potential independent launch
- Phase 3 studies continue evaluating olezarsen in broader
patient population with severe hypertriglyceridemia
(SHTG)
- Ionis to host webcast today at 11
a.m. ET
CARLSBAD, Calif., Sept. 26,
2023 /PRNewswire/ -- Ionis Pharmaceuticals,
Inc. (Nasdaq: IONS) today announced positive topline results
for the Phase 3 Balance study of olezarsen in people with familial
chylomicronemia syndrome (FCS). The trial met its primary efficacy
endpoint with a statistically significant reduction in triglyceride
(TG) levels with the olezarsen 80
mg monthly dose at six months
compared to placebo (p=0.0009); triglyceride lowering continued to
improve at 12 months. In addition, olezarsen 80 mg showed a 100
percent reduction in acute pancreatitis events compared to placebo
(0 events for olezarsen versus 11 events for placebo), a key
secondary endpoint.
Treatment with olezarsen 80 mg resulted in a >75% reduction
in apoC-III, a protein produced in the liver that regulates TG
metabolism in the blood. In addition to the 80 mg monthly dose, the
study also evaluated a lower 50 mg monthly dose. Olezarsen
demonstrated a dose-dependent effect, with both study doses showing
a substantial reduction in pancreatitis. The lower 50 mg dose did
not reach statistical significance at six months on the primary
endpoint of triglyceride lowering (p=0.0775).
Ionis plans to file a New Drug Application in early 2024 with
the U.S. Food and Drug Administration (FDA) in addition to EU
regulatory filings. If approved, olezarsen would be the first
available treatment in the U.S. for FCS, a rare, debilitating
genetic disease that can lead to acute, potentially fatal
pancreatitis attacks. The FDA granted olezarsen Fast Track
designation for the treatment of FCS in 2023, which is designed to
expedite the FDA's review of innovative, new drugs that demonstrate
the potential to address unmet medical need. Ionis will present the
Phase 3 olezarsen FCS data at a future medical congress.
"These positive olezarsen topline results represent an important
advance for people with FCS who live in constant fear of
unpredictable and potentially fatal attacks of acute pancreatitis.
With no currently FDA-approved treatments, people with FCS live
with debilitating abdominal pain and must maintain an extremely
restrictive diet consisting of less than 20 grams of fat per day,"
said Sam Tsimikas, M.D., senior vice
president, global cardiovascular
development at Ionis. "In this study, people with FCS treated with
olezarsen along with background therapy and a low-fat diet had a
substantially reduced risk of recurrent attacks of acute
pancreatitis. These results strengthen our confidence in
olezarsen's potential to deliver benefits to FCS patients and in
the larger population with SHTG following completion of ongoing
Phase 3 studies."
Olezarsen demonstrated a favorable safety and tolerability
profile in the study. There were more adverse events in the placebo
group compared to the olezarsen groups, primarily due to
pancreatitis events. The majority of adverse events in the
olezarsen groups were mild in severity. There was a low incidence
of injection site reactions. No hepatic or renal toxicity events
occurred and there were no clinically meaningful platelet reductions. One death was reported in the
study, which was deemed as not related to study drug.
"Today is a proud moment in our company's evolution, as
olezarsen is poised to be a long-awaited advance for FCS patients
and Ionis' first potential independent commercial launch," said
Brett P. Monia, Ph.D., chief
executive officer of Ionis. "We believe olezarsen has the potential
to become the new standard of care for patients with FCS and
we are excited about its potential
in the broader population of patients with SHTG where we have
ongoing pivotal trials. We want to express our gratitude to the
patients, caregivers, investigators and study teams who
participated in the Balance study. We look forward to submitting
these data to the FDA and anticipate that olezarsen will be the
first of many medicines from our wholly owned pipeline that we
bring to people with debilitating diseases."
Webcast
Ionis will conduct a webcast today at 11:00 a.m. Eastern
time to discuss this announcement. Interested parties may access
the webcast here. A webcast replay will be available for a limited
time at the same address. Visit www.ionispharma.com for more
information and to register.
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
triglyceride levels at 12 months and adjudicated acute pancreatitis
event rate.
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). Because of limited LPL
production or function, people with FCS cannot break down
chylomicrons, lipoprotein particles that are 90% triglycerides. FCS
is estimated to impact 1-2 people per million worldwide. People
living with FCS are at high risk for acute pancreatitis in addition
to other chronic health issues such as fatigue and severe,
recurrent abdominal pain. They are sometimes unable to work, adding
to their disease burden.
Currently, there are no FDA-approved therapies for the treatment
of FCS. People living with this condition currently rely solely on
nutrition management through extremely restrictive diets to
navigate the health risks associated with FCS.
About Olezarsen
Olezarsen is an investigational LIgand Conjugated
Antisense (LICA) medicine being evaluated for people at risk
of disease due to elevated triglyceride (TG) levels including those
with familial chylomicronemia syndrome, or FCS. Olezarsen is
designed to inhibit the body's production of apoC-III, a protein
produced in the liver that regulates TG metabolism in the blood.
The FDA granted olezarsen Fast Track designation for the treatment
of FCS in Q1 2023. In addition to FCS, Ionis is evaluating
olezarsen for the treatment of severe hypertriglyceridemia (SHTG)
in Phase 3 clinical trials.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been a leader in RNA-targeted
therapy, pioneering new markets and changing standards of care.
Ionis currently has four marketed medicines and a promising
late-stage pipeline highlighted by cardiovascular and neurological
franchises. Our scientific innovation began and continues with the
knowledge that sick people depend on us, which fuels our vision to
become the leader in genetic medicine, utilizing a multi-platform
approach to discover, develop and deliver life-transforming
therapies.
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
olezarsen, Ionis' technologies 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 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, 2022, and the most
recent Form 10-Q quarterly filing, which are on file with the
Securities and Exchange Commission. 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" all refer to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a registered trademark of Ionis
Pharmaceuticals, Inc.
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SOURCE Ionis Pharmaceuticals, Inc.