- NEURO-TTRansform study met all co-primary and secondary
endpoints
- Positive results to be presented today at AAN 2023
demonstrate eplontersen efficacy, safety and administration profile
may provide an important new treatment option in this fatal disease
with significant unmet need
- Ionis to host webcast on Tuesday,
April 25 at 1 p.m. ET
CARLSBAD, Calif., April 24,
2023 /PRNewswire/ -- Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS) today announced that the Phase 3 NEURO-TTRansform
study for AstraZeneca and Ionis' eplontersen in patients with
hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN)
met all co-primary endpoints and secondary endpoints at 66 weeks
versus an external placebo group. The positive results are being
presented today in an Emerging Science Session at the American
Academy of Neurology (AAN) 2023 Annual Meeting in Boston. ATTRv-PN is a debilitating disease
driven by the progressive accumulation of TTR amyloid deposits,
which causes progressive nerve damage and leads to organ failure
and eventually death.
At 66 weeks, patients treated with eplontersen demonstrated
consistent and sustained benefit on the three co-primary
endpoints measuring serum transthyretin (TTR) concentration,
neuropathy impairment and quality of life:
- Eplontersen achieved a least squares (LS) mean reduction of 82%
in serum TTR concentration from baseline, compared to an 11%
reduction from baseline in the external placebo group
(p<0.0001).
- Eplontersen halted disease progression as measured by modified
Neuropathy Impairment Score +7 (mNIS+7), resulting in a 0.28 point
LS mean increase compared to a 25.06 point increase for the
external placebo group from baseline (24.8 point LS mean
improvement; p<0.0001).
-
- Overall, 47% of treated patients showed improvements in
neuropathy at 66 weeks compared to baseline versus 17% in the
external placebo group. Among study completers, 53% of treated
patients showed improvements in neuropathy at 66 weeks compared to
baseline versus 19% in the external placebo group.
- Eplontersen improved quality of life demonstrating a 5.5 point
LS mean decrease (improvement) on the Norfolk Quality of Life
Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), compared to a
14.2 point increase (worsening) in the external placebo group (19.7
point LS mean improvement; p<0.0001).
-
- Overall, 58% of treated patients showed improvements in QoL at
66 weeks compared to baseline versus 20% in the external placebo
group. Among study completers, 65% of treated patients showed
improvements in QoL at 66 weeks compared to baseline versus 23% in
the external placebo group.
- Eplontersen demonstrated statistically significant benefits on
both mNIS+7 and Norfolk QoL-DN at 35 weeks versus the external
placebo, which were further improved at 66 weeks.
Eplontersen achieved statistically significant improvements in
all secondary endpoints versus the external placebo group.
Eplontersen continued to demonstrate a favorable safety and
tolerability profile. The rate of treatment emergent adverse events
in the eplontersen group was comparable to the external placebo
group across all major categories. There were no adverse events of
special interest that led to study drug discontinuation.
"In the past, patients with hereditary transthyretin amyloid
polyneuropathy usually deteriorated given the limited available
treatments. This new study shows eplontersen can halt progression
of neuropathy and improve quality of life at 66 weeks when compared
to placebo," said Sami Khella, M.D.,
chief, department of neurology at Penn Presbyterian Medical Center,
professor of clinical neurology at the Perelman School of Medicine
at the University of Pennsylvania
School of Medicine and a principal investigator on the
NEURO-TTRansform study. "Today's important results demonstrate that
eplontersen has a consistent and sustained treatment effect and
reinforces its potential as an important medicine for the thousands
of patients living with this debilitating and fatal disease."
"In the NEURO-TTRansform study, we were encouraged to see a
substantial number of patients treated with eplontersen improved in
measures of neuropathy impairment and quality of life at both the
interim and final analyses," said Eugene
Schneider, M.D., executive vice president and chief clinical
development officer for Ionis. "We and our partners at AstraZeneca
are especially grateful to the patients who participated in this
study. With our potential approval in the U.S. in December and
plans to file for regulatory approval in the EU and other
countries, we are looking forward to potentially bringing
eplontersen to ATTRv-PN patients in this largely underrecognized
global patient population."
The NEURO-TTRansform Emerging Science presentation and poster at
AAN can be found on Ionis' website after today's AAN presentation
at 11:57 a.m. ET.
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. The U.S. Food and Drug Administration
accepted the New Drug Application for eplontersen for the treatment
of ATTRv-PN with a PDUFA action date of December 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-mediated 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.
Webcast
Ionis will host a webcast to discuss the detailed 66-week
results from the NEURO-TTRansform study on Tuesday, April 25 at 1
p.m. ET. Interested parties may access the webcast here. A
webcast replay will be available for a limited time.
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 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 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 168 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 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.
Editor's Note: The NEURO-TTRansform study was funded by
AstraZeneca and Ionis. Dr. Khella reports research support from and
scientific advisory board participation with AstraZeneca, and
compensation for serving as a consultant for Ionis.
Ionis Pharmaceuticals® is a trademark of Ionis
Pharmaceuticals, Inc.
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SOURCE Ionis Pharmaceuticals, Inc.