- Donidalorsen met the primary endpoint with a statistically
significant reduction in the rate of HAE attacks in patients
treated every 4 weeks or patients treated every 8
weeks
- Donidalorsen demonstrated a favorable safety and
tolerability profile
- Ionis is preparing to submit a New Drug Application with
U.S. FDA
- Data to be presented at an upcoming medical
congress
CARLSBAD, Calif., Jan. 22,
2024 /PRNewswire/ -- Ionis Pharmaceuticals,
Inc. (Nasdaq: IONS) today announced positive topline results
for the Phase 3 OASIS-HAE study of donidalorsen in people with
hereditary angioedema (HAE). The trial met its primary endpoint of
reduction in rate of angioedema attacks in patients treated with
donidalorsen (80mg) via subcutaneous injection dosed every 4 weeks
(Q4W) (p<0.001) or every 8 weeks (Q8W) (p=0.004), compared to
placebo. In addition, the trial showed donidalorsen achieved
statistical significance on all secondary endpoints in the Q4W
group and key secondary endpoints in the Q8W group. Donidalorsen
demonstrated a favorable safety and tolerability profile in the
study, and there were no serious adverse events in the patients
treated with donidalorsen.
HAE is a rare and life-threatening genetic disease that causes
unpredictable and frequent severe swelling of the skin,
gastrointestinal (GI) tract, upper respiratory system, face and
throat. Donidalorsen is an investigational RNA-targeted
prophylactic medicine designed to precisely target and silence the
production of prekallikrein (PKK), interrupting the pathway that
leads to HAE attacks.
Based on these data, Ionis is preparing to submit a New Drug
Application with the U.S. Food and Drug Administration. Otsuka,
which has exclusive rights to commercialize donidalorsen in
Europe, is preparing to submit a
Marketing Authorization Application to the European Medicines
Agency. Donidalorsen received Orphan Drug Designation in the U.S.,
and the Orphan Drug Designation procedure in the EU is ongoing.
"We are very pleased with the positive topline results from the
Phase 3 OASIS-HAE study of donidalorsen," said Kenneth Newman, M.D., senior vice president,
head of clinical development at Ionis. "Based on these results and
the durable efficacy and favorable safety data seen in the ongoing
Phase 2 open-label extension study, we believe donidalorsen, if
approved, could be an attractive new treatment option for patients
with HAE, many of whom continue to experience unpredictable,
painful and severe breakthrough attacks despite currently available
prophylactic treatments. We are grateful to the patients,
caregivers, investigators and study teams who participated in the
OASIS-HAE study."
"These data represent our third highly positive Phase 3 readout
over the last 12 months, underscoring the strength of our LICA
platform for RNA-targeted medicines," said Brett P. Monia, Ph.D., chief executive officer
of Ionis. "Following the recent launch of WAINUA™ (eplontersen), we
are now well on our way to independently launching medicines from
our wholly owned pipeline with regulatory submissions this year for
olezarsen in familial chylomicronemia syndrome and donidalorsen in
HAE. These achievements, coupled with our robust R&D pipeline,
position Ionis to continue to deliver a steady cadence of
potentially transformational medicines to people with serious
diseases for years to come."
Ionis plans to present the Phase 3 OASIS-HAE results at an
upcoming medical congress by mid-year. Ionis also plans to share
results from the Phase 3 OASIS-Plus study by mid-year, which
includes both the open-label extension of the Phase 3 trial and a
separate cohort of patients who have transitioned to donidalorsen
from another prophylactic HAE medication (switch cohort).
About the OASIS-HAE Study
The global, multicenter, randomized, double-blind,
placebo-controlled Phase 3 OASIS-HAE study (NCT05139810) enrolled
91 participants, age 12 and above, with Type 1 and Type 2
hereditary angioedema (HAE). Participants were randomized in a 2:1
ratio to receive donidalorsen 80 mg or placebo via subcutaneous
injection once every four weeks for 24 weeks or donidalorsen 80 mg
or placebo via subcutaneous injection once every eight weeks for 24
weeks. Within each cohort, participants were randomized in a 3:1
ratio to receive donidalorsen or matching-placebo. The primary
endpoint was the time-normalized number of investigator-confirmed
HAE attacks from week one to week 25 compared to placebo. More than
90% of patients completed the OASIS-HAE study. Following completion
of the treatment period, over 90% of randomized patients entered
the Phase 3 OASIS-Plus open-label extension study.
About the OASIS-Plus Study
The Phase 3 OASIS-Plus open-label extension (OLE) study is a
53-week global, multicenter study of subcutaneous injections of
donidalorsen administered every four weeks (80mg) and every eight
weeks (80mg) in patients completing the OASIS-HAE trial. These are
patients aged 12 and above, with Type 1 and Type 2 hereditary
angioedema (HAE). The study is designed to evaluate the safety and
efficacy of extended dosing of donidalorsen following completion of
the Phase 3 OASIS-HAE study. The OASIS-Plus switch cohort is
evaluating the safety and efficacy of long-term dosing of
donidalorsen every four weeks in patients who were previously
treated with another prophylactic HAE medication. Additional
information about OASIS-Plus (NCT04307381) may be found at
ClinicalTrials.gov.
About Hereditary Angioedema (HAE)
HAE is a rare and life-threatening genetic disease characterized
by unpredictable and frequently severe swelling of the skin,
gastrointestinal (GI) tract, upper respiratory system, face, and
throat, which can be life-threatening1,2,3,4,5. HAE is
estimated to affect more than 20,000 people in the U.S. and
Europe6. In the U.S.,
doctors frequently use prophylactic treatment approaches to prevent
and reduce the severity of HAE attacks in patients.
About Donidalorsen
Donidalorsen is an RNA investigational
LIgand-Conjugated Antisense (LICA) medicine
designed to precisely target and silence the production of
prekallikrein (PKK), interrupting the pathway that leads to HAE
attacks. PKK plays an important role in activating inflammatory
mediators associated with acute attacks of hereditary angioedema
(HAE). By silencing the production of PKK, donidalorsen could be an
effective prophylactic approach to treating HAE.
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 five 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 X (Twitter) @ionispharma and LinkedIn.
Ionis' Forward-looking Statements
This press release includes forward-looking statements regarding
Ionis' business and the therapeutic and commercial potential of
donidalorsen, 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.
1 Manning ME. Dermatol Ther (Heidelb). 2021;
11:1829-1838.
2 Valerieva A, et al. Balkan Med J. 2021;8:89-103.
3 Santacroce R, et al. J Clin Med.
2021;10:2023.
4 Pines JM, et al. J Emerg Med. 2021;60:35-43.X
5 Maurer M, et al. World Allergy Organ J.
2022;15:100627.
6 Weller K, et al. Allergy. 2016;71(8):
1203-1209.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/ionis-announces-positive-topline-results-from-phase-3-oasis-hae-study-of-investigational-donidalorsen-in-patients-with-hereditary-angioedema-302040172.html
SOURCE Ionis Pharmaceuticals, Inc.