- Donidalorsen delivered significant and sustained reductions in
HAE attacks, with high levels of disease control and improvement in
quality of life measures with monthly or every two-month dosing;
continued attack rate reduction over time
- In first-of-its-kind prospective analysis, patients switching
from prior prophylactic treatment to donidalorsen experienced
further reductions in mean monthly HAE attack rates from
baseline
- Donidalorsen demonstrated a favorable safety and tolerability
profile across all cohorts
- Data to be presented today at EAACI Congress 2024
- Ionis to host webcast on Friday, May
31 at 8:00am ET
CARLSBAD, Calif., May 31, 2024
/PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today
announced positive results from the Phase 3 OASIS-HAE and OASISplus
studies of donidalorsen in patients with hereditary angioedema
(HAE) demonstrating significant and sustained reduction in mean
monthly HAE attack rates and continued attack rate improvement of
>90% with one year of treatment for both monthly or every
two-month dosing. Patients who switched to donidalorsen from prior
prophylactic treatment also showed 62% further reduction in mean
monthly HAE attack rates from baseline, and 84% of patients who
switched reported a preference for donidalorsen. Donidalorsen had a
favorable safety and tolerability profile across both studies,
including when self-administered via an auto-injector. Results will
be presented in three late-breaking oral presentations at the
2024 European Academy of Allergy and Clinical Immunology
(EAACI) Annual Congress in Valencia, Spain. Based on these data, Ionis is
pursuing regulatory approval of donidalorsen as a potential
treatment for HAE.
HAE is a rare and potentially life-threatening genetic condition
that involves recurrent attacks of severe swelling (angioedema) in
various parts of the body, including the hands, feet, genitals,
stomach, face and/or throat. Donidalorsen is an investigational
RNA-targeted prophylactic medicine designed to reduce the
production of prekallikrein (PKK), interrupting the pathway that
leads to HAE attacks.
"We're delighted by the results from the OASIS clinical program,
which we believe position donidalorsen to advance the prophylactic
treatment paradigm for people living with HAE. Despite currently
available therapies, people living with HAE still face significant
disease burden and new prophylactic treatments are needed," said
Brett Monia, Ph.D., chief executive
officer of Ionis. "These data underscore the potential of
donidalorsen to continually improve HAE attack rates and quality of
life over time, positioning donidalorsen as an attractive potential
treatment option. In our prospective switch cohort, patients
switched to donidalorsen from another prophylactic without
increased breakthrough attacks and achieved greater disease
control. In fact, a majority of patients who switched reported a
preference for donidalorsen. We thank the patients, families and
clinicians who participated in these important studies. Based on
these results, Ionis will pursue regulatory approval for
donidalorsen, and we look forward to launching it as part of our
growing independent commercial pipeline, if approved."
OASIS-HAE Study Results
In the Phase 3 OASIS-HAE
study, patients with HAE were treated with donidalorsen (80 mg) via
subcutaneous injection every four weeks (Q4W) (n=45) or every eight
weeks (Q8W) (n=23), or placebo (n=22), over 24 weeks.
- The study met its primary endpoint, demonstrating 81% lower
monthly HAE attack rate with donidalorsen Q4W compared to placebo
over weeks one to 25 (p<0.001), and 55% reduction with Q8W
(p=0.004).
- In weeks five to 25, donidalorsen Q4W significantly reduced
mean monthly HAE attack rates by 87% (p<0.001) compared to
placebo, a key secondary endpoint.
- In the same time frame, treatment with donidalorsen Q4W reduced
severe to moderate attacks per month by 89% (p<0.001).
- Donidalorsen Q4W also reduced HAE attacks that require acute
therapy by 92% (p<0.001).
- At week 25, 91% of donidalorsen Q4W patients were
well-controlled as measured by the Angioedema Control Test (AECT).
- Donidalorsen resulted in clinically significant improvement in
quality of life as measured by the Angioedema Quality of Life
Questionnaire (AE-QoL).
- Donidalorsen Q8W had a similar benefit as Q4W dosing over time
on attack rate reduction and quality of life measures.
- Donidalorsen was well-tolerated, with no serious treatment
emergent adverse events (TEAEs) related to donidalorsen. Most
adverse events (AEs) were mild or moderate in severity, and
injection site reactions were the most common AE. One patient in
the donidalorsen Q8W group discontinued based on investigator
recommendation due to patient noncompliance and a TEAE.
OASISplus Study Results – Open-Label Extension and
Switch
The OASISplus study included an open-label
extension (OLE) cohort and a first-of-its-kind
prospective cohort to assess patients switching from both newer
oral and injectable long-term prophylactic treatments to
donidalorsen.
Open-Label Extension Cohort
Following completion of
the placebo-controlled treatment period in OASIS-HAE, 94% of
eligible patients enrolled in the OLE cohort. Participants
continued to receive treatment with donidalorsen via subcutaneous
injection dosed every four weeks (n=69) or every eight weeks
(n=14). As of the February 28, 2024
data cut:
- Attack rates continued to improve over time, resulting in 93%
and 92% improvement from baseline measured at the start of
OASIS-HAE across Q4W and Q8W, respectively.
- Extended treatment resulted in further improved quality of life
measures and high levels of disease control.
- At week 25, 91% (Q4W) and 100% (Q8W) of patients reported
well-controlled disease as measured by the AECT.
- AE-QoL scores improved by 28 points (Q4W) and 24 points (Q8W)
at week 25 compared to baseline in OASIS-HAE. An improvement of 6
points is considered clinically meaningful.
- Safety results were consistent with findings from OASIS-HAE,
with no serious safety concerns and no patient
discontinuations.
Switch Cohort
The OASISplus switch cohort evaluated
the safety and efficacy of long-term dosing of donidalorsen every
four weeks in patients (n=64) who were previously treated with
another prophylactic HAE medication (lanadelumab, berotralstat or
C1-esterase inhibitor) for at least 12 weeks prior to entering the
study. Patients followed a pre-defined specific protocol to
transition from their prior therapy to donidalorsen. Results from a
pre-defined endpoint of 17 weeks indicate:
- Patients switched to donidalorsen from prior prophylactic
treatment without an increase in breakthrough attacks.
- Patients experienced a 62% further improvement in mean monthly
HAE attack rate compared to baseline for previous prophylactic
treatment.
- 84% of patients who switched reported a preference for
donidalorsen over their previous treatment, citing better disease
control, less time to administer, and less injection site pain or
reactions.1
- Quality of life measures also showed continued improvement,
with 93% of patients reporting well-controlled disease compared to
67% at baseline with prior prophylactic treatment. Results also
demonstrated ≥8-point improvement in AE-QoL scores.
- Safety results were consistent with findings from OASIS-HAE,
with no serious safety concerns. One patient discontinued due to
TEAE not related to donidalorsen.
"People living with HAE are facing a lifelong battle, and I see
that impact firsthand in my practice. It's critical for treatment
options to have lasting, durable efficacy," said Marc Riedl, M.D., M.S. clinical director, U.S.
HAEA Angioedema Center; clinical service chief, Division of Allergy
& Immunology, University of California,
San Diego. "The OASISplus study demonstrated patients are
able to change therapy to donidalorsen without the risk of
increased breakthrough HAE attacks while continuing to improve in
measures of quality of life and disease control."
"The comprehensive OASIS clinical program demonstrates how
donidalorsen can potentially address key concerns patients may
experience with currently available treatment options," said
Kenneth Newman, M.D., senior vice
president of clinical development at Ionis. "Donidalorsen
significantly reduced HAE attack rates, and with the simplicity of
monthly or every two-month self-administration via autoinjector, we
believe that donidalorsen has a unique profile that may address the
needs of people with HAE."
Ionis plans to file a New Drug Application this year with the
U.S. Food and Drug Administration (FDA), marking progress toward
the goal of launching our second wholly owned medicine. Otsuka
Pharmaceutical Co., Ltd., which has exclusive rights to
commercialize donidalorsen in Europe, is also preparing to submit a
Marketing Authorization Application to the European Medicines
Agency this year.
All presentations can be found on Ionis' website after today's
presentations at 10:45am ET.
Webcast
Ionis will hold a webcast today at
8:00am ET to discuss this update.
Interested parties may access the webcast here. A webcast replay
will be available for a limited time.
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 HAE-1 and HAE-2 hereditary angioedema. Participants were
randomized in a 2:1 ratio to receive donidalorsen (80mg) or placebo
via subcutaneous injection once every four weeks for 24 weeks or
donidalorsen (80mg) 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. Following completion of the treatment
period, 94% of eligible patients entered the Phase 3 OASISplus
open-label extension study.
About the OASISplus Study
The Phase 3 OASISplus
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 study.
These are patients aged 12 and above, with HAE-1 and HAE-2
hereditary angioedema. 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 OASISplus 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 OASISplus (NCT04307381) may be found
at ClinicalTrials.gov.
About Hereditary Angioedema (HAE)
HAE is a rare
and potentially life-threatening genetic condition that involves
recurrent attacks of severe swelling (angioedema) in various parts
of the body, including the hands, feet, genitals, stomach, face
and/or throat.2,3,4,5,6 HAE is estimated to
affect more than 20,000 patients in the U.S. and
Europe.7
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 investigational
LIgand-Conjugated Antisense (LICA) medicine
designed to target prekallikrein (PKK), which plays an important
role in activating inflammatory mediators associated with acute
attacks of hereditary angioedema (HAE). By reducing the production
of PKK, donidalorsen could be an effective prophylactic approach to
preventing HAE attacks.
About Ionis Pharmaceuticals, Inc.
For three decades,
Ionis has invented medicines that bring better futures to people
with serious diseases. Ionis currently has five marketed medicines
and a leading pipeline in neurology, cardiology, and other areas of
high patient need. As the pioneer in RNA-targeted medicines, Ionis
continues to drive innovation in RNA therapies in addition to
advancing new approaches in gene editing. A deep understanding of
disease biology and industry-leading technology propels our work,
coupled with a passion and urgency to deliver life-changing
advances for patients.
To learn more about Ionis, visit Ionispharma.com and follow us
on X (Twitter) and LinkedIn.
Ionis Forward-looking
Statements
This press release includes forward-looking
statements regarding Ionis' business, financial guidance and the
therapeutic and commercial potential of our commercial medicines,
donidalorsen, additional medicines in development and technologies.
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 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. Except as required by law, we
undertake no obligation to update any forward-looking statements
for any reason. 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,
2023, and most recent Form 10-Q, 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.
Ionis Investor Contact:
D. Wade Walke, Ph.D.
info@ionisph.com 760-603-2331
Ionis Media Contact:
Hayley
Soffer
CorporateCommunications@ionisph.com 760-603-4679
- Patients selected a reason for switching from a predefined list
of reasons.
- Manning ME. Dermatol Ther (Heidelb). 2021; 11:1829-1838.
- Valerieva A, et al. Balkan Med J. 2021;8:89-103.
- Santacroce R, et al. J Clin Med. 2021;10:2023.
- Pines JM, et al. J Emerg Med. 2021;60:35-43.X
- Maurer M, et al. World Allergy Organ J. 2022;15:100627.
- Weller K, et al. Allergy. 2016;71(8): 1203-1209.
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