- Continued treatment over two years with donidalorsen
demonstrated sustained reduction in hereditary angioedema attacks
and improved quality of life
- Donidalorsen recently received orphan drug designation in
the U.S.
- Topline Phase 3 results expected in H1 2024
CARLSBAD, Calif., Nov. 9, 2023
/PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today
announced positive results from an ongoing Phase 2 open-label
extension (OLE) study evaluating the safety and efficacy of its
investigational prophylactic medicine, donidalorsen, in patients
with hereditary angioedema (HAE), a rare and life-threatening
genetic disease. Over the two years, patients treated with
donidalorsen via subcutaneous injection showed an overall sustained
mean reduction in HAE attack rates of 96% from baseline, from 2.70
to 0.06 attacks per month, across all dosing
groups. Furthermore, all patients treated with donidalorsen
reported a clinically meaningful improvement in quality of life as
measured by the Angioedema Quality of Life Questionnaire (AE-QoL)
over two years. Treatment with donidalorsen was well tolerated in
the studies, and there were no serious adverse events.
"Hereditary angioedema is a significant healthcare challenge for
which there is an ongoing need for long-term, sustained
prophylactic treatment offering patients significant efficacy and
tolerability that is easy to use," said Richard S. Geary, Ph.D., executive vice
president and chief development officer at Ionis. "We are very
encouraged by the demonstrated safety, efficacy, and quality of
life profile of donidalorsen. The two-year OLE results further
support donidalorsen as a potentially compelling prophylactic
treatment option for patients with hereditary angioedema. We
look forward to reporting pivotal topline Phase 3 results in the
first half of next year."
Following the 13-week blinded, placebo-controlled Phase 2 study,
patients were eligible for enrollment in the OLE study. Of the 20
Phase 2 study participants, 17 entered the OLE study and were on a
fixed 13-week dosing period where they received donidalorsen
80 mg every four weeks. From week 17 through two years, patients
entered a flexible dosing period where they either received
donidalorsen 80 mg every four weeks, 80 mg every eight weeks, or
100 mg every four weeks.
In a subset analysis also presented at the American College
of Allergy, Asthma & Immunology (ACAAI) Annual Scientific
Meeting, 62.5% of patients receiving donidalorsen 80 mg every eight
weeks remained attack-free over the two-year period and had a
sustained mean reduction in HAE attack rates of 83% from baseline.
Injection site (IS) discoloration and IS reaction were the only
study drug-related treatment-emergent adverse events (TEAEs)
reported in more than one patient (n=2, 11.8% each). No serious
adverse events were reported in the OLE study, and no TEAEs led to
study discontinuation.
The poster presentations about the Phase 2 Open-Label Extension
Study and the sub-analysis of the eight-week dosing
arm are available on the ACAAI website.
About Phase 2 Open-Label Extension Study
- An open-label extension study of donidalorsen in up to 24
participants, age 18 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 administered subcutaneously (SC),
with 80 mg every four- or eight weeks and 100 mg every four
weeks.
- Additional information about the Phase 2 open-label extension
study (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-threatening1-5.
- HAE is estimated to affect more than 20,000 patients 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 investigational
LIgand-Conjugated Antisense (LICA) medicine
designed to target the prekallikrein, or PKK, pathway.
- PKK plays an important role in activating inflammatory
mediators associated with acute attacks of hereditary angioedema
(HAE).
- To reduce the production of PKK, donidalorsen could be an
effective prophylactic approach to preventing HAE attacks.
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
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 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, and most recent
Form 10-Q, which are on file with the SEC. Copies of these and
other documents are available at www.ionispharma.com.
Ionis Pharmaceuticals® is a registered trademark of Ionis
Pharmaceuticals, Inc.
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- 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.
- 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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