- Publication of NEURO-TTRansform study in patients with
hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN)
showed eplontersen halted disease progression and continuously
improved quality of life at 35-, 66- and 85-week analyses
- Data demonstrates consistent and sustained benefit on all
co-primary and secondary endpoints
CARLSBAD, Calif., Sept. 28,
2023 /PRNewswire/ -- Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS) today announced that The Journal of the
American Medical Association (JAMA) published positive
results from the Phase 3 NEURO-TTRansform study of eplontersen, an
investigational treatment for hereditary transthyretin-mediated
amyloid polyneuropathy (ATTRv-PN).
Results from the week 66 primary analysis showed that
eplontersen-treated patients demonstrated improvement across all
co-primary and secondary endpoints, including serum transthyretin
(TTR) concentration, neuropathy impairment and quality of life,
compared to the external placebo group. An end-of-treatment
analysis also showed eplontersen continued to demonstrate sustained
improvements through 85 weeks.
"The totality of positive, consistent eplontersen data position
this therapy, which can be self-administered, to be an important
and empowering potential new medicine for treating hereditary
transthyretin-mediated amyloid polyneuropathy," 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
trial. "Without treatment, hereditary transthyretin-mediated
amyloid polyneuropathy is a debilitating and devasting disease that
can ultimately result in death. The JAMA publication reinforces the
growing body of evidence showing that eplontersen significantly
reduces serum transthyretin concentration, may halt progression of
neuropathy impairment, and improves overall patient quality of
life, providing hope to this community."
"These data reinforce the ability of eplontersen to halt disease
progression and improve quality of life throughout the 19-month
treatment period," said Eugene
Schneider, M.D., executive vice president and chief clinical
development and operations officer for Ionis. "We look forward to
the upcoming FDA action date in December and bringing eplontersen
to this underserved patient community in the U.S. and around the
world."
In the NEURO-TTRansform Phase 3 study, patients treated with
eplontersen demonstrated consistent and sustained benefit on the
three co-primary endpoints of serum transthyretin (TTR)
concentration, neuropathy impairment measured by modified
Neuropathy Impairment Score +7 (mNIS+7) and quality of life (QoL)
on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy
(Norfolk QoL-DN):
- Eplontersen achieved a least squares (LS) mean reduction of 82%
in TTR serum concentration from baseline at 65 weeks compared to an
11% reduction from baseline in the external placebo group
(p<0.001).
- Eplontersen demonstrated statistically significant benefits on
both mNIS+7 and Norfolk QoL-DN at 35 weeks versus the external
placebo group, which were further improved at 66 weeks. Eplontersen
halted disease progression as measured by modified Neuropathy
Impairment Score +7 (by modified mNIS+7), resulting in a 0.3 point
LS mean increase at week 66 compared to a 25.1 point increase for
the external placebo group from baseline (24.8 point LS mean
improvement; p<0.001). 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.
- In addition, eplontersen improved QoL (on Norfolk QoL-DN),
demonstrating a 5.5 point LS mean decrease at 66 weeks
(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<0.001). 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 also achieved statistically significant
improvements in all secondary endpoints versus the external placebo
group through 66 weeks and 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.
Results from the end-of-treatment analysis showed eplontersen
provided sustained improvements through 85 weeks. Eplontersen
continued to demonstrate a sustained reduction in serum TTR
concentration, continued to halt disease progression as measured by
the mNIS+7, and demonstrated continued improvement in QoL as
measured by the Norfolk QoL-DN, all compared to baseline.
Ionis and AstraZeneca presented the results from the 35- and
66-week analyses as an Emerging Science presentation at the
American Academy of Neurology Annual Meeting in April. The results
from the 85-week end-of-treatment analysis of the trial will be
submitted to an upcoming medical meeting.
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. This agreement was recently expanded
to include exclusive rights for AstraZeneca to commercialize
eplontersen in Latin America and
all other countries outside the U.S. Eplontersen was granted Orphan
Drug Designation in the U.S. The U.S. Food and Drug Administration
(FDA) granted a PDUFA action date of Dec.
22, 2023.
Eplontersen is currently being evaluated in the
CARDIO-TTRansform Phase 3 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.
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)
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 at week 35, week 66 and week 85. The final analysis
comparing eplontersen to an external placebo group was completed at
week 66. All patients were then followed on treatment until week 85
and evaluated four weeks after the last dose in an end-of-trial
assessment. Following treatment and the end-of-trial assessments,
patients were eligible to enter an open-label extension study to
continue receiving eplontersen once every four weeks or enter a
20-week post-treatment evaluation period. 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.
Ionis currently has four 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
eplontersen, Ionis' technologies 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
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, and the most
recent Form 10-Q quarterly filing, 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.
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SOURCE Ionis Pharmaceuticals, Inc.