- Zilganersen is the first investigational medicine in
clinical development for people with Alexander disease, a rare,
life-threatening neurological condition
CARLSBAD, Calif., July 18,
2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS) announced today that it has completed
enrollment in the pivotal trial of zilganersen (ION373), an
investigational RNA-targeted medicine in development for the
treatment of children and adults with a rare, progressive and
ultimately fatal neurological disorder known as Alexander disease
(AxD). The primary endpoint is percent change from baseline in gait
speed as assessed by the 10-Meter Walk Test (10MWT). Topline data
are anticipated in the second half of 2025.
AxD is estimated to occur in an estimated one in one million
people in the U.S. and can present throughout life.1-3
The disease is a result of genetic variants in the glial
fibrillary acidic protein (GFAP) gene that disrupt the
structure and function of astrocytes in the brain. AxD is generally
characterized by cognitive dysfunction and progressive neurologic
deterioration, including loss of independence and the ability to
control muscles for large movements, swallowing and airway
protection. Zilganersen is designed to stop the excess GFAP that
accumulates because of disease-causing variants in the GFAP
gene, with the goal of slowing or stabilizing disease progression
in people living with AxD.
"Current approaches to disease management for Alexander disease
can mitigate some symptoms of AxD but do not address the underlying
cause or slow disease progression. Our zilganersen study is
the first trial to evaluate an investigational medicine designed to
address the underlying cause of Alexander disease," said Eugene
Schneider, M.D., executive vice president and chief clinical
development officer at Ionis. "We are grateful for the dedication
and support from the patients, families and investigators in the
Alexander disease community, whose partnership has made this
milestone possible."
About the Zilganersen Study
The global, multicenter, randomized, double-blind, controlled,
multiple-ascending dose (MAD) is a Phase 1-3 study (NCT04849741),
which enrolled patients aged two to 65 with Alexander disease (AxD)
across 13 sites in eight countries. Participants were randomized in
a 2:1 ratio to receive zilganersen or control for a 60-week
double-blind treatment period. At 60 weeks, all participants will
receive zilganersen for a 180-week open-label treatment period,
followed by a 28-week post-treatment follow-up period. The primary
endpoint is percent change from baseline in gait speed as assessed
by the 10-Meter Walk Test (10MWT) at the end of the double-blind
treatment period. Secondary endpoints include change from baseline
in patients' self-identified Most Bothersome Symptom (MBS) Score,
Patient Global Impression of Severity (PGIS) Score, Patient Global
Impression of Change (PGIC) Score and Clinician Global Impression
of Change (CGIC) Score at the end of the double-blind treatment
period.
The study includes an open-label sub-study in eligible
participants under the age of two years with AxD, which will
continue to enroll into 2025.
About Zilganersen (ION373)
Zilganersen is an
investigational antisense oligonucleotide medicine being developed
as a potential treatment for people with genetically confirmed
Alexander disease (AxD). Zilganersen is designed to stop the excess
glial fibrillary acidic protein (GFAP) production that accumulates
because of disease-causing variants in the GFAP gene. In
2020, the U.S. Food and Drug Administration (FDA) granted
zilganersen Orphan Drug designation and Rare Pediatric designation.
In addition, the European Medicines Agency (EMA) granted
zilganersen Orphan Drug designation in 2019.
About Alexander Disease (AxD)
AxD is a rare, progressive and ultimately fatal neurological
disease that affects a type of cell in the brain called astrocytes.
Astrocytes have multiple roles in the brain to support neurons and
oligodendrocytes, including maintenance of the myelin sheath that
protects nerve fibers. AxD is caused by disease-causing variants in
the glial fibrillary acidic protein (GFAP) gene and is
generally characterized by cognitive dysfunction and progressive
neurologic deterioration, including loss of independence and the
ability to control muscles for large movements, swallowing and
airway protection, though symptoms can vary depending on age of
onset. AxD usually leads to death within 14-25 years after symptom
onset. There are no disease modifying medicines approved for
patients.
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 Ionis.com and follow us on
X (Twitter) and LinkedIn.
Ionis Forward-looking
Statements
This press release includes forward-looking
statements regarding Ionis' business, and the therapeutic and
commercial potential of Ionis' commercial medicines, zilganersen,
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.Ionis.com.
In this press release, unless the context requires otherwise,
"Ionis," "Company," "we," "our" and "us" all refer to Ionis
Pharmaceuticals and its subsidiaries.
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Ionis Pharmaceuticals, Inc.
Ionis Investor Contact:
D. Wade Walke, Ph.D.
IR@ionis.com - 760-603-2331
Ionis Media Contact:
Hayley Soffer
Media@ionis.com - 760-603-4679
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1 Li R,
Johnson AB, Salomons G, et al. Glial fibrillary acidic protein
mutations in infantile, juvenile, and adult forms of Alexander
disease. Ann Neurol. 2005;57(3):310-326.
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2 Pareyson
D, Fancellu R, Mariotti C, et al. Adult-onset Alexander disease: a
series of eleven unrelated cases with review of the literature.
Brain. 2008;131(Pt 9):2321-2331.
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3 Yoshida T,
Mizuta I, Saito K, et al. Effects of a polymorphism in the GFAP
promoter on the age of onset and ambulatory disability in
late-onset Alexander disease. J Hum Genet.
2013;58(9):635-638.
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SOURCE Ionis Pharmaceuticals, Inc.