European Approval of Donidalorsen Expands RNA-Targeted Prevention Strategies for HAE

The European Commission (EC) has granted marketing authorization for donidalorsen (Dawnzera, Otsuka Pharmaceuticals), a subcutaneously administered prophylactic therapy for the routine prevention of hereditary angioedema (HAE) attacks in adults and adolescents aged 12 years and older. The decision applies across all 27 European Union member states, as well as Iceland, Liechtenstein, and Norway (1).

The authorization introduces a new RNA-targeted prophylactic therapy option that targets the disease pathway upstream of symptom onset. Donidalorsen, a ligand-conjugated antisense oligonucleotide, is designed to reduce hepatic production of prekallikrein, a key component of the plasma kallikrein–kinin cascade that is responsible for bradykinin-mediated swelling attacks (2,3).

“We are proud of the decision from the European Commission to authorize the use of donidalorsen in HAE,” said Andy Hodge, president and CEO at Otsuka Pharmaceutical Europe, in a Jan. 21, 2026, company press release. “This represents another key milestone in the collaboration between Otsuka and Ionis which aims to address unmet need in a challenging rare disease.”

How does European approval reshape treatment options for HAE?

HAE is a rare genetic disorder characterized by recurrent, unpredictable swelling episodes that may affect the extremities, abdomen, face, or airway. These attacks can be painful, debilitating, and in some cases life-threatening.

Disease onset frequently occurs in childhood, with approximately half of patients experiencing symptoms by age 10, underscoring the need for effective long-term preventive therapies (4–6). Clinical evidence supporting the EC’s decision came from a Phase III randomized, double-blind, placebo-controlled trial involving 90 participants.

Patients who received 80 mg of donidalorsen every four weeks experienced an 81% reduction in four-weekly attack rates compared with placebo over 24 weeks, according to Otsuka. The company reported that dosing every eight weeks also demonstrated efficacy, producing a 55% reduction in attack rates relative to placebo (1).

Why are the Phase III outcomes significant for RNA-targeted therapies in rare diseases?

From an industry perspective, this approval highlights the growing maturity of RNA-targeted approaches in rare disease prophylaxis. Antisense oligonucleotides have historically faced challenges related to delivery, dosing frequency, and long-term safety monitoring.

The demonstrated efficacy at both four- and eight-week dosing intervals suggests increasing flexibility in treatment regimens, which may influence future development strategies for chronic rare conditions. The European authorization builds on regulatory momentum established in the United States, where donidalorsen received FDA approval in August 2025 for prophylactic use in patients aged 12 years and older (7).

Commercialization in Europe is supported through a licensing collaboration initiated between Otsuka and Ionis in 2023 and later expanded to the Asia-Pacific region (1).

Why does this approval matter for biopharma development and manufacturing?

Beyond its clinical implications, EC’s approval underscores how advances in nucleic acid chemistry, conjugation technologies, and manufacturing controls are enabling more consistent large-scale production of complex oligonucleotide therapies (8). As rare disease pipelines increasingly incorporate RNA-based modalities, regulatory approvals such as this one may accelerate investment in specialized manufacturing capacity and global supply infrastructure.

References

1. Otsuka Pharmaceutical. Dawnzera (donidalorsen) Granted European Union Marketing Authorization for the Prevention of Hereditary Angioedema. Press Release. Jan. 21, 2026.
2. Riedl, M. A.; Tachdjian, R.; Lumry, W. R.; et al. Efficacy and Safety of Donidalorsen for Hereditary Angioedema. N. Engl. J. Med. 2024, 391 (1), 21–31. DOI:10.1056/NEJMoa2402478
3. Riedl, M. A.; Yarlas, A.; Bordone, L.; et al. Patient-Reported Outcomes in the Phase III OASIS-HAE Study of Donidalorsen for Hereditary Angioedema. Allergy (Oxford, U. K.) 2025, 80 (8), 2361–2368. DOI: 10.1111/all.16563
4. Raasch, J.; Glaum, M. C.; O'Connor, M. The Multifactorial Impact of Receiving a Hereditary Angioedema Diagnosis. World Allergy Organ. J. 2023,16 (6),100792. DOI: 10.1016/j.waojou.2023.100792 
5. HAE International. Attack Triggers: Most HAE Attacks Occur Spontaneously. haei.org (accessed Jan. 21, 2026).
6. Chong-Neto, H. J. A Narrative Review of Recent Literature of the Quality of Life in Hereditary Angioedema Patients. World Allergy Organ. J. 2023, 16 (3), 100758. DOI: 10.1016/j.waojou.2023.100758
7. Ionis Pharmaceuticals. DAWNZERA (donidalorsen) Approved in the US as First and Only RNA-Targeted Prophylactic Treatment for Hereditary Angioedema. Press Release. Aug. 21, 2025.
8. Obexer, R.; Nassir, M.; Moody, E. R.; et al. Modern Approaches to Therapeutic Oligonucleotide Manufacturing. Science 2024, 384 (6692), eadl4015. DOI: 10.1126/science.adl4015