Full Press Release Details
Ionis presents positive results from OASIS-HAE and OASISplus studies of investigational medicine donidalorsen in patients with hereditary angioedema
CARLSBAD, Calif., May 31, 2024 -- 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.
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:
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:
"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.
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.
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.
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.
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