Donidalorsen Shows Promise as Prophylactic Treatment for Hereditary Angioedema


Patients administered donidalorsen experienced a lower hereditary angioedema (HAE) attack rate, which indicates the potential for prophylactic use in treating HAE.

Image credit: ZayNyi |

Image credit: ZayNyi |

The results of the Phase III OASIS-HAE (NCT05139810) clinical trial and OASISplus open-label extension (OLE) trial show that patients administered donidalorsen (Ionis Pharmaceuticals) experienced a reduced hereditary angioedema (HAE) attack rate, suggesting its potential for prophylactic use in treating the disease, according to the investigators.1,2 A novel ligand-conjugated antisense medication, donidalorsen was developed to target prekallikrein, which has been implicated in activating inflammatory mediators linked to acute HAE attacks.2

“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,” Brett Monia, PhD, chief executive officer of Ionis, said in a press release. “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.”2

The global, multicenter, randomized, double-blind, placebo-controlled OASIS-HAE trial enrolled 91 patients aged 12 years and older, with HAE-1 and HAE-2 hereditary angioedema. Patients were randomly assigned in a 2:1 ratio to receive donidalorsen (80 mg) or placebo via subcutaneous (SC) injection once every four weeks for 24 weeks or donidalorsen (80 mg) or placebo SC injection once every eight weeks for 24 weeks.

Patients in each cohort were randomly assigned in a 3:1 ratio to receive donidalorsen or matching-placebo. The trial’s primary endpoint was time-normalized number of investigator-confirmed HAE attacks starting at week one through 25 weeks compared with placebo. After completing treatment, 94% of eligible participants were enrolled in the Phase III OASISplus OLE portion.

A total of 45 patients were administered donidalorsen every four weeks, 23 were administered donidalorsen every eight weeks, and 22 patients were administered placebo. The results showed a least-squares mean time-normalized attack rate of 0.44 (95% CI, 0.27 to 0.73) among the four-week cohort, 1.02 (95% CI, 0.65 to 1.59) in the eight-week cohort, and 2.26 (95% CI, 1.66 to 3.09) in the placebo cohort.1

The mean attack rate starting at week one through week 25 was 81% lower (95% CI, 65 to 89) among patients in the four-week cohort compared to the placebo cohort (P<0.001) and 55% lower (95% CI, 22 to 74) in the eight-week cohort compared to the placebo cohort (P=0.004). Further, median decrease in attack rate from baseline was 90% in the four-week cohort, 83% in the eight-week cohort, and 16% in the placebo cohort.

Mean attack rate from weeks five to 25 was 87% lower (95% CI, 72 to 94) in the four-week cohort than the placebo cohort (P<0.001) and 60% lower (95% CI, 25 to 79) in the eight-week cohort than the placebo cohort. Patients in the every four-week cohort experienced an improved least-squares mean total score for change at week 25 on the Angioedema Quality-of-Life Questionnaire that was 18.6 points (95% CI, 9.5 to 27.7) better than patients in the placebo (P<0.001) cohort.

The most frequently reported adverse events (AEs) among patients administered donidalorsen were erythema at the injection site, headache, and nasopharyngitis, with 98% of AEs deemed mild or moderate in severity.

Ionis stated that it will file a New Drug Application with the FDA this year for donidalorsen in the treatment of HAE.2

“The comprehensive OASIS clinical program demonstrates how donidalorsen can potentially address key concerns patients may experience with currently available treatment options,” said Kenneth Newman, MD, 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.”2


1. Riedl M. Efficacy and Safety of Donidalorsen for Hereditary Angioedema. N Engl J Med 2024;391:21-31 DOI: 10.1056/NEJMoa2402478. VOL. 391 NO. 1.

2. Ionis presents positive results from OASIS-HAE and OASISplus studies of investigational medicine donidalorsen in patients with hereditary angioedema. News release. Ionis Pharmaceuticals. May 31, 2024. Accessed July 8, 2024.

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