- Positive End of Phase 2 discussion with FDA, including
alignment on Phase 3 design
- Bayley-4 expressive communication selected as Phase 3 study
primary endpoint
- Initiation of ION582 Phase 3 study planned for H1 2025
- Ionis to share ION582 program update at the FAST Global Science
Summit in November
CARLSBAD, Calif., Nov. 6, 2024
/PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS)
today announced the pivotal Phase 3 study design following
successful alignment with the U.S. Food and Drug Administration
(FDA) on ION582, an investigational medicine for the treatment of
people living with Angelman syndrome (AS). AS typically presents in
infancy and is characterized by profound intellectual disability,
impaired verbal abilities and severe motor impairment.
"Following positive results for ION582 in the Phase 2 HALOS
trial, we are pleased to have alignment with the FDA on the design
of our Phase 3 REVEAL trial, which will address clinical endpoints
that reflect the most pressing and meaningful outcomes for people
living with AS and their caregivers," said Brett Monia, Ph.D., chief executive officer of
Ionis. "We will enroll a broad group of individuals living with AS
in the global pivotal Phase 3 trial, planned to begin in the first
half of 2025. We look forward to working with the community to
advance a potential new treatment targeting the underlying cause of
disease in this debilitating neurological condition that has no
approved medicines."
The planned global, randomized, placebo-controlled Phase 3 study
will enroll approximately 200 children and adults with AS that have
a maternal UBE3A gene deletion or mutation. The primary
analysis will occur after approximately one year of treatment,
followed by all patients transitioning into an open-label long-term
extension (LTE) phase of the study. Patients will be randomized 2:1
to active therapy or placebo, and ION582 will be evaluated at two
dose levels which will be dosed quarterly without a loading
regimen. The primary endpoint will be improvement in expressive
communication as assessed by the Bayley Scales for Infant and
Toddler Development-4 (Bayley-4), an objective and direct
clinician-administered assessment of clinical functioning. Deficits
in expressive communication are reported to be the symptoms most
challenging to caregivers of people with AS. The study will
evaluate several secondary endpoints including overall disease
severity, cognition, communication, sleep, motor functioning and
daily living skills, in addition to other exploratory
endpoints.
The End of Phase 2 meeting was supported by data from the Phase
2 open-label HALOS study. In the recently completed multiple
ascending dose (MAD) portion of the study, ION582 treatment
provided strong evidence of clinically meaningful
improvement on all functional domains including communication,
cognition and motor function. Overall, 97% of people in the medium
and high dose groups assessed in the study saw an improvement in
overall AS symptoms as measured by the Angelman Syndrome Clinical
Global Improvement Change (SAS-CGI-C) scale, which evaluates
clinicians' impressions. ION582 showed favorable safety and
tolerability at all dose levels in the study.
At the FAST Global Science Summit this weekend (November 8-9), Ionis will provide an update to
the community on the Phase 3 program and review data from the MAD
portion of the HALOS trial.
About ION582
ION582 is an investigational antisense medicine designed to
inhibit the expression of the UBE3A antisense transcript
(UBE3A-ATS) and increase production of UBE3A protein, for the
potential treatment of Angelman syndrome (AS). In 2022, the U.S.
Food and Drug Administration (FDA) granted ION582 Orphan Drug
designation and Rare Pediatric designation.
About Angelman Syndrome (AS)
AS is a rare, genetic neurological disease caused by the loss of
function of the maternally inherited UBE3A gene. AS typically
presents in infancy and is characterized by profound intellectual
disability, balance issues, motor impairment and debilitating
seizures. Most patients are unable to speak. Individuals with AS
have a normal lifespan but require complete care from a caregiver.
Some symptoms can be managed with existing medicines; however,
there are no approved disease modifying therapies.
About Ionis' Neurology Franchise
Ionis has been at the forefront of discovering
and developing leading neurological disease medicines, including
SPINRAZA® (nusinersen), the first approved treatment for
spinal muscular atrophy, WAINUA™ (eplontersen), a medicine to
treat hereditary transthyretin-mediated amyloid polyneuropathy
(ATTRv-PN), and QALSODY® (tofersen) for SOD1-ALS. The
clinical-stage portfolio includes 11 therapies, of which five are
wholly owned by Ionis. Ionis' investigational portfolio includes
medicines for which there are few or no disease modifying
treatments, such as rare diseases including Prion disease and
Alexander disease and more common conditions such as Alzheimer's
and Parkinson's disease.
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), LinkedIn and Instagram.
Ionis Forward-looking
Statements
This press release includes forward-looking statements regarding
Ionis' business, and the therapeutic and commercial potential of
Ionis' commercial medicines, ION582 and Ionis' 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.
Ionis Pharmaceuticals® is a registered trademark of
Ionis Pharmaceuticals, Inc.
ION582 is an investigational medicine that has not been approved
for the treatment of any disease by regulatory
authorities.
Ionis Pharmaceuticals Investor Contact: D. Wade
Walke, Ph D. - IR@ionis.com - 760-603-2331
Ionis Pharmaceuticals Media Contact: Hayley Soffer - Media@ionis.com -
760-603-4679
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SOURCE Ionis Pharmaceuticals, Inc.