- Eplontersen met co-primary endpoints demonstrating sustained
reduction in TTR and benefits in neuropathy and quality of life
through 66 weeks
- 35 and 66-week data to be presented at the American Academy of
Neurology (AAN) Annual Meeting in April
CARLSBAD, Calif., March 27,
2023 /PRNewswire/ -- Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS) today announced positive topline results from the
66-week analysis of the Phase 3 NEURO-TTRansform study of Ionis and
AstraZeneca's eplontersen in patients with hereditary
transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), a
debilitating and potentially fatal disease that leads to peripheral
nerve damage and motor disability.
At 66 weeks, patients treated with eplontersen continued to
demonstrate a statistically significant and clinically meaningful
change from baseline versus an external placebo group on the
co-primary endpoints of modified Neuropathy Impairment Score +7
(mNIS+7), a measure of neuropathic disease progression, and Norfolk
Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).
The study also met its third co-primary endpoint demonstrating a
statistically significant reduction in serum TTR concentration
versus an external placebo group. TTR reductions were consistent
with those reported at week 35. Eplontersen continued to
demonstrate a safety and tolerability profile consistent with that
observed at 35 weeks.
"The positive results from the 66-week analysis of the Phase 3
NEURO-TTRansform trial show that eplontersen provided consistent
and sustained transthyretin protein reduction and that a
substantial number of patients improved in measures of both
neuropathy progression and quality of life," said Sami Khella, M.D., chief, department of
neurology, Penn Presbyterian Medical Center and professor of
clinical neurology, University of
Pennsylvania School of Medicine. "This builds on the
favorable 35-week results, which first demonstrated eplontersen's
potential to significantly improve outcomes in this underserved
population."
"These latest results from our NEURO-TTRansform study
represent an important step towards delivering a potential new
therapy for ATTRv-PN patients living with this debilitating and
fatal disease. We are encouraged by the sustained benefit
demonstrated by eplontersen and what a self-administered treatment
could mean for patients and families affected by ATTRv-PN," said
Eugene Schneider, M.D., executive
vice president and chief clinical development officer for Ionis.
"Together with our partner AstraZeneca, we look forward to sharing
detailed results from this study at the upcoming American Academy
of Neurology Annual Meeting."
"These results further underscore eplontersen's potential to be
a best-in-class treatment across all forms of
transthyretin-mediated amyloidosis, including polyneuropathy and
cardiomyopathy which can lead to heart failure," said Mene Pangalos, executive vice president,
BioPharmaceuticals R&D, AstraZeneca. "With limited treatment
options currently available, there is an urgent unmet medical need
for new therapies and earlier, accurate diagnosis across the
different types of this systemic, progressive and fatal
condition."
Data from both the 35 and 66-week analyses will be presented as
an Emerging Science presentation at the American Academy of
Neurology (AAN) Annual Meeting in April. The initial results from
the 35-week analysis were presented at the International Symposium
on Amyloidosis meeting in September
2022.
As part of a global development and commercialization agreement,
Ionis and AstraZeneca are seeking regulatory approval for
eplontersen for the treatment of ATTRv-PN in the U.S. and plan to
seek regulatory approval in Europe
and other parts of the world. Earlier this month, the U.S. Food and
Drug Administration accepted a New Drug Application for eplontersen
for the treatment of ATTRv-PN with a PDUFA action date of
Dec. 22, 2023. Eplontersen was
granted Orphan Drug Designation in the U.S.
Eplontersen is currently being evaluated in the Phase 3
CARDIO-TTRansform study for transthyretin amyloid cardiomyopathy
(ATTR-CM), a systemic, progressive and fatal condition that
typically leads to progressive heart failure and often death within
three to five years from disease onset.
About the NEURO-TTRansform
Study
NEURO-TTRansform is a global, open-label, randomized trial
evaluating the efficacy and safety of eplontersen in patients with
ATTRv-PN. The trial enrolled adult patients with ATTRv-PN Stage 1
or Stage 2 and up to week 66 eplontersen is being compared to the
external placebo group from the NEURO-TTR registrational trial for
inotersen that Ionis completed in 2017. The final analysis
comparing eplontersen to external placebo was completed at week 66
and all patients will be followed on treatment until week 85, when
they will have the option to transition into an open-label
extension study. For more information on the NEURO-TTRansform
study, please visit:
https://clinicaltrials.gov/ct2/show/NCT04136184
About Hereditary
Transthyretin-Mediated Amyloid Polyneuropathy (ATTRv-PN)
Hereditary transthyretin-mediated amyloid polyneuropathy
(ATTRv-PN) is caused by the accumulation of misfolded mutated TTR
protein in the peripheral nerves. Patients with ATTRv-PN experience
ongoing debilitating nerve damage throughout their body resulting
in the progressive loss of motor functions, such as walking. These
patients also accumulate TTR in other major organs, which
progressively compromises their function. The damage from misfolded
TTR protein accumulation leads to disability within five years of
diagnosis and is generally fatal within a decade.
About Eplontersen
Eplontersen is an investigational
LIgand-Conjugated Antisense
(LICA) medicine designed to inhibit the production of TTR
protein. Eplontersen is being developed as a monthly
self-administered subcutaneous injection to treat all types of
ATTR. ATTR amyloidosis is a systemic, progressive and fatal disease
in which patients experience multiple overlapping clinical
manifestations caused by the inappropriate formation and
aggregation of TTR amyloid deposits in various tissues and organs,
including peripheral nerves, heart, intestinal tract, eyes,
kidneys, central nervous system, thyroid and bone marrow. The
progressive accumulation of TTR amyloid deposits in these tissues
and organs leads to organ failure and eventually death.
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 with
its novel antisense technology. Ionis currently has three 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
Ionis' technologies, eplontersen 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 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. 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, which is on file
with the Securities and Exchange Commission. Copies of this and
other documents are available from the Company.
In this press release, unless the context requires otherwise,
"Ionis," "Company," "we," "our," and "us" refers to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a trademark of Ionis
Pharmaceuticals, Inc.
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SOURCE Ionis Pharmaceuticals, Inc.