– Treatment with donidalorsen in Phase 2 study
significantly reduced angioedema attacks by 90% and provided
improvement in quality of life
– Published findings demonstrate favorable safety and
tolerability profile of donidalorsen in Phase 2 study
– Donidalorsen is one of Ionis' wholly owned medicines the
company plans to commercialize
CARLSBAD, Calif., March 16, 2022 /PRNewswire/ -- Ionis
Pharmaceuticals, Inc. (Nasdaq: IONS), the leader in RNA-targeted
therapies, today announced the publication of positive Phase 2 data
for donidalorsen (formerly IONIS-PKK-LRx) in the New
England Journal of Medicine (NEJM) available at NEJM.org.
Donidalorsen is an investigational antisense medicine Ionis is
evaluating for treating patients with hereditary angioedema (HAE).
In the Phase 2 study, donidalorsen demonstrated a 90% reduction in
angioedema attacks compared with placebo at the 80 mg monthly dose.
There was significant improvement in quality of life as assessed by
the Angioedema Quality of Life Questionnaire (AE-QoL) in the
patients treated with donidalorsen.
Experience the interactive Multichannel News Release here:
https://www.multivu.com/players/English/9020351-ionis-pharmaceuticals-announces-publication-of-positive-phase-2-data-for-donidalorsen-in-nejm/
Donidalorsen is designed to reduce the production of
prekallikrein, which plays a key role in the activation of
inflammatory mediators associated with acute attacks of HAE.
Donidalorsen uses Ionis' advanced
LIgand-Conjugated Antisense (LICA)
technology platform.
"Positive Phase 2 data published in NEJM, along with data
presented at the American Academy of Allergy, Asthma &
Immunology (AAAAI) Annual Meeting, demonstrate that treatment
with donidalorsen reduced attack frequency and disease burden
of hereditary angioedema," said Kenneth Newman, M.D., M.B.A.,
Ionis' vice president of clinical development and leader of the
immunology and pulmonology franchise. "The promising findings from
this study are particularly encouraging as we continue to advance
the Phase 3 clinical study for donidalorsen and underscore our
commitment to deliver transformative treatments for patients with
unmet therapeutic needs."
The Phase 2 study is double-blind and placebo-controlled in
which patients with hereditary angioedema due to C1-inhibitor
deficiency were randomized 2:1 to either 80 mg
donidalorsen (n=14) or placebo (n=6) administered
subcutaneously every 4 weeks for 16 weeks. The primary
endpoint was the number of monthly angioedema attacks between weeks
1 and 17. Secondary endpoints included the time-normalized number
of all, and only moderate or severe, angioedema attacks per month
between weeks 5 and 17 and quality of life, measured with the
AE-QoL. In this study, donidalorsen was safe and well
tolerated.
The mean monthly rate of angioedema attacks was 0.23 (95%
confidence interval (CI), 0.08 to 0.39) and 2.21 (95% CI, 0.58 to
3.85) in patients receiving donidalorsen and placebo, respectively
(mean difference, -90%; 95% CI, -76 to -96%; P<0.001). The mean
attack rate between Weeks 5 and 17 was 0.07 (95% confidence
interval CI, -0.08 to 0.23) and 2.06 (95% CI, 0.41 to 3.72) in
patients receiving donidalorsen and placebo, respectively (mean
difference, -97%; 95% CI, -69 to –100%).
Patients reported higher overall health-related quality of life
(HRQoL) over 17 weeks with donidalorsen, with a mean change in
total score of the AE-QoL of -26.85, compared with -6.15 in the
placebo group (P=0.002) where reduction in the score indicates
better quality of life. There were improvements observed across all
individual domains of the AE-QoL compared with placebo.
The majority of adverse events during the study were mild
with a frequency that was similar between patients receiving
donidalorsen and placebo groups. There were no deaths or serious
adverse events. The most common treatment-emergent adverse events
(TEAEs) reported in patients treated with donidalorsen were
headache (14.3%) and nausea (7.1%), both of which occurred at a
higher incidence in the placebo group. None of the patients
discontinued treatment due to adverse events.
In addition to publication in NEJM, three abstracts
analyzing data from the Phase 2 study were presented at the
American Academy of Allergy, Asthma & Immunology Annual Meeting
(#AAAAI22) in late February:
Abstract #493: Pharmacodynamics and
Pharmacokinetics of PKK-LRx in Patients with Hereditary
Angioedema
Plasma prekallikrein (PKK) plays a key role in the activation of
inflammatory mediators associated with acute attacks of HAE. The
pharmacodynamics and pharmacokinetics of donidalorsen were
evaluated in the Phase 2 study.
Treatment resulted in a robust reduction of plasma PKK (mean
reduction of about 65%), with a significant reduction starting two
weeks after the first dose. The reduction in plasma PKK correlated
with clinical improvement in HAE attacks.
Abstract #494: An Open-label Trial with Plasma
Prekallikrein Oligonucleotide Antisense Therapy to Control
Angioedema Attacks in Hereditary Angioedema Patients with Normal
C1-inhibitor
Hereditary angioedema with nC1-INH-HAE (Type 3) is a very rare
condition, characterized by recurrent and unpredictable swellings
which are disabling and potentially fatal. There are currently no
approved prophylactic treatments for this condition.
An additional group of three patients with nC1-INH-HAE were
evaluated in a parallel-arm, open-label study of donidalorsen.
Compared to baseline, the attack frequency was lower in all three
patients, and one patient was free of attacks from Week 1 to Week
17.
The mean monthly attack rate was 4.23 (95% confidence interval
[CI] -2.56 to 11.03) at baseline and 1.52 during the treatment
period (95% CI -3.99 to 7.04); mean difference -76%
(95% confidence interval: -146.45 to -5.59). Treatment with
donidalorsen was well tolerated with no severe adverse events.
Abstract #506: The Impact on Quality of Life
Following Treatment with Plasma Prekallikrein Targeted
Oligonucleotide Antisense Therapy in Hereditary Angioedema
Patients
The impact of donidalorsen on HRQoL was a predefined endpoint in
the Phase 2 trial, assessed with the validated AE-QoL at
randomization and the end of study.
Patients reported higher overall HRQoL over 17 weeks with
donidalorsen, with a mean change in total score of the AE-QoL of
-26.85, compared with -6.15 in the placebo group (P=0.002) where
reduction in the score indicates better quality of life. There were
improvements observed across all individual domains of the AE-QoL
compared with placebo.
About Hereditary Angioedema
HAE is a rare and potentially fatal genetic disease that is
characterized by rapid and painful attacks of inflammation in the
hands, feet, limbs, face, abdomen, larynx, and trachea. HAE affects
approximately 20,000 patients in the U.S. and Europe and can be fatal if swelling occurs in
the larynx. In patients with frequent or severe attacks, doctors
may use prophylactic treatment approaches to prevent and reduce the
severity of HAE attacks.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been the 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 premier late-stage pipeline
highlighted by industry-leading cardiovascular and neurological
franchises. Our scientific innovation began and continues with the
knowledge that sick people depend on us, which fuels our vision of
becoming a leading, fully integrated biotechnology company.
To learn more about Ionis,
visit www.ionispharma.com and follow us on Twitter
@ionispharma.
Ionis Forward-looking
Statement
This press release includes forward-looking statements regarding
Ionis' business, and the therapeutic and commercial potential of
Ionis' technologies, donidalorsen 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 the impact COVID-19 could
have on our business, and 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 December 31, 2021, and the most recent Form 10-Q
quarterly filing, which are on file with the SEC. Copies of
these and other documents are available from the Company.
View original
content:https://www.prnewswire.com/news-releases/ionis-announces-publication-of-positive-phase-2-data-for-donidalorsen-in-new-england-journal-of-medicine-301504607.html
SOURCE Ionis Pharmaceuticals, Inc.