- ION582 demonstrated consistent improvements across multiple
functional domains in Angelman syndrome patients
- ION582 was safe and well tolerated at all dose
levels
- Ionis plans to move ION582 into pivotal trial
- Detailed ION582 data to be presented at upcoming medical
meeting
CARLSBAD, Calif., May 16, 2024
/PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq:
IONS) today announced positive topline data from the HALOS
Phase 1/2a open-label study of ION582 in Angelman syndrome. ION582
was safe and well tolerated in the study and showed encouraging and
consistent benefits in individuals living with Angelman syndrome,
with the most robust improvements observed in key areas of
functioning including cognition, communication and motor
function.
Ionis also announced that it will independently advance ION582
as part of Ionis' leading portfolio of potentially transformational
medicines for serious neurological diseases. Ionis plans to review
the ION582 Phase 1/2a results with regulatory authorities to align
on the design of the pivotal program. Biogen has elected not to
exercise its option to license ION582.
"There are currently no approved treatments for Angelman
syndrome, which causes developmental delays, cognitive impairment
and severe communications challenges, with most individuals unable
to speak or live independently," said Lynne
Bird, M.D., professor of clinical pediatrics at UC San Diego
and HALOS study investigator. "We are encouraged by the positive
and consistent improvements seen in the HALOS study across multiple
measures, as these functional improvements could have a
transformative impact in the lives of people living with Angelman
syndrome and their caregivers. We are also encouraged by the
favorable safety and tolerability profile observed in the study,
which is particularly important when treating children. We very
much look forward to further evaluation of ION582 in a pivotal
program."
Angelman syndrome is caused by a loss of function in the
maternal UBE3A gene. ION582 is designed to unsilence the paternal
UBE3A allele in order to increase production of the UBE3A protein
in the brain. Angelman syndrome affects an estimated one in 12,000
to 20,000 people globally.1 It presents as profound and
severe developmental delays in motor, language and cognitive
functioning, seizures and ataxia. It is a
serious neurodevelopmental disorder that presents in early
childhood, resulting in complete dependence on a caregiver.
"We are encouraged by the data from the HALOS study and pleased
to add this promising medicine to our growing independent pipeline
of neurology medicines," said Brett Monia, Ph.D., chief
executive officer of Ionis. "We look forward to sharing detailed
data at the upcoming Angelman Syndrome Foundation meeting and to
advancing ION582 into a pivotal study. Individuals with Angelman
syndrome face significant neuro-developmental challenges and have
no approved therapies today. We are committed to working closely
with the community, investigators and regulators to advance this
promising investigational medicine."
Part 1 of the HALOS trial was a three-month, multiple-ascending
dose (MAD) study in 51 patients aged 2-50, which evaluated three
doses of ION582. All eligible patients transitioned into the Part 2
long-term extension (LTE) portion of the study, which is evaluating
the two higher doses of ION582 for an additional 12 months. Part 3
of the study will evaluate eligible patients for an additional
three years. Topline results were available for all patients at
four months (one month after last MAD dose), and six months, and
were consistent with preliminary findings reported at the
Foundation for Angelman Syndrome Therapeutics (FAST) meeting in
November 2023. Topline data
included:
- Safety assessment was the primary objective of the trial and
ION582 was safe and well tolerated at all dose levels. Adverse
events in the trial were consistent with patient medical histories,
Angelman syndrome diagnosis or related to intrathecal
administration.
- ION582 showed consistent effects across multiple objective and
subjective measures used to assess functioning in individuals
living with Angelman syndrome. These include the Bayley-4, an
objective physician assessment of clinical functioning, Angelman
Syndrome Clinical Global Improvement Change (SAS-CGI-C) scale,
which evaluates clinicians' impressions, and the Vineland-3 and
Observer-Reported Communication Ability (ORCA) measures, which are
parent-reported assessment tools. These positive results correlated
with positive changes in EEG activity including a reduction in slow
wave delta activity.
- At six months, approximately 65% of patients achieved an
improvement in cognition on the Bayley-4. While no direct
comparisons should be made, these improvements exceeded
improvements seen in natural history studies over the same time
period.
- At six months, approximately 70% of patients showed improvement
on Bayley-4 measures of receptive and/or expressive communication.
While no direct comparisons should be made, these changes exceeded
improvements seen in natural history studies over the same time
period.
- At six months, approximately 65% of patients showed
improvements in Bayley-4 measures of fine and gross motor skills.
While no direct comparisons should be made, these changes exceeded
improvements seen in natural history studies over the same time
period.
Ionis expects to report detailed results from the HALOS study at
the Angelman Syndrome Foundation meeting in July. ION582 has
received Orphan Drug designation in the U.S. The HALOS Phase
1/2a open-label trial is evaluating safety, tolerability,
pharmacokinetics and pharmacodynamics in addition to certain
clinical outcomes measures. ION582 is administered intrathecally
into the cerebral spinal fluid with a lumbar puncture. For more
information on the HALOS Study (NCT05127226),
visit clinicaltrials.gov.
About Ionis' Neurology Franchise
Ionis' neurology franchise addresses all major brain regions and
central nervous system cell types and currently has three Phase 3
studies ongoing with 11 therapies in clinical development, several
of which Ionis plans to commercialize directly. Ionis is
discovering and developing potential treatments for many
neurological diseases for which there are few or no disease
modifying treatments, including common diseases like Alzheimer's
and Parkinson's as well as rare diseases such as amyotrophic
lateral sclerosis (ALS) and Alexander disease. Ionis has discovered
and developed three commercially available neurological disease
medicines, including SPINRAZA® (nusinersen), the first approved
treatment for spinal muscular atrophy, WAINUATM
(eplontersen), a medicine to treat hereditary
transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and
QALSODY® (tofersen) for SOD1-ALS.
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.
Ionis Forward-looking
Statements
This press release includes forward-looking
statements regarding Ionis' business, financial guidance and the
therapeutic and commercial potential of our commercial medicines,
ION582, 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 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 December 31,
2023, and most recent Form 10-Q, 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. QALSODY® is a registered
trademark of Biogen. WAINUATM is a registered trademark
of the AstraZeneca group of companies.
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
1 Mertz LG, Christensen R, Vogel I, Hertz JM, Nielsen
KB, Gronskov K, Ostergaard JR. Angelman syndrome in Denmark. birth incidence, genetic findings,
and age at diagnosis. Am J Med Genet A. 2013;161A:2197–203.
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