Donidalorsen Shows Promise Reducing HAE Attacks Ahead of August PDUFA

The phase 3 OASISplus prospective switch study found patients with hereditary angioedema (HAE) who switched from prophylactic treatments to donidalorsen had a 62% further reduction in the mean monthly HAE attack rate.1

Ionis Pharmaceuticals announced this promising pivotal data on July 21, 2025, following the news on November 4, 2024, of the US Food and Drug Administration (FDA) accepting the New Drug Application (NDA) for donidalorsen to prevent attacks of HAE in adult and pediatric patients aged ≥ 12 years and assigning a target date of August 21, 2025.2

“In this study, we saw that patients were able to switch to donidalorsen from another prophylactic without an increase in attacks, and in fact, there was a reduction in mean attack rate,” said Kenneth Newman, MD, senior vice president, clinical development, at Ionis, in a statement.1 “This translated to meaningful improvements in quality of life and disease control compared to baseline with their prior treatment.”

HAE is a rare, potentially life-threatening condition involving angioedema in various parts of the body—hands, feet, genitals, stomach, face, or throat—and affects > 20,000 patients in the US and Europe. Donidalorsen, an investigational medicine designed to target prekallikrein, activates inflammatory mediators linked to acute attacks of HAE. It offers a prophylactic approach to preventing HAE attacks.

The phase 3 OASISplus study included an open-label extension cohort of patients who completed the OASIS-HAE trial. The study also included a prospective cohort to evaluate patients switching from oral and injectable long-term prophylactic treatments to donidalorsen.

The OASISplus switch cohort assessed the efficacy and safety of donidalorsen administered every 4 weeks in patients who previously received lanadelumab (n = 32), C1-esterase inhibitor (n = 22), or berotralstat (n = 11) for ≥ 12 weeks before the trial. Patients entered a 10-week baseline period where they stayed on their previous HAE prophylactic therapy before switching to donidalorsen.

The team observed no mean increase in breakthrough attacks during the switch. After 16 weeks of donidalorsen treatment, patients experienced a 62% overall further reduction in mean HAE attack rate compared to their previous prophylactic treatment at baseline. The HAE attack rate reduced by 73%, 65%, and 41% for patients switching from berotralstat, lanadelumab, and C1INH, respectively.

Most (84%) patients reported a preference for donidalorsen over their previous therapy. Better disease control, less time to administer, and less injection site pain or reactions swayed patients’ preferences. Most participants (93%) reported well-controlled disease after switching to donidalorsen, compared to baseline (67%), as seen on the Angioedema Control Test (AECT).

Participants well tolerated donidalorsen, with no serious treatment-emergent adverse events (TEAEs). Most adverse events were mild or moderate in severity, with injection site reactions being the most common. Only 1 patient discontinued due to a TEAE, although it was not related to donidalorsen.

“The study was designed to provide patients and physicians with data to inform switching to donidalorsen,” Newman added. “The results support our belief that donidalorsen has the potential to be the prophylactic treatment of choice for HAE, if approved.”

References

1. Phase 3 OASISplus data demonstrating benefit of donidalorsen for HAE patients who switched from other prophylactics published in JACI In Practice. Business Wire. July 21, 2025. https://www.businesswire.com/news/home/20250721310278/en/Phase-3-OASISplus-data-demonstrating-benefit-of-donidalorsen-for-HAE-patients-who-switched-from-other-prophylactics-published-in-JACI-In-Practice. Accessed July 21, 2025.

2. Ionis announces FDA acceptance of New Drug Application for donidalorsen for prophylactic treatment of HAE. Ionis. November 4, 2024. https://ir.ionis.com/news-releases/news-release-details/ionis-announces-fda-acceptance-new-drug-application-donidalorsen. Accessed July 21, 2025.