Dawnzera (donidalorsen sodium) / Ionis, Otsuka, Theratechnologies - LARVOL DELTA

Donidalorsen Treatment in Children With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=20 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Switching Long-Term Prophylaxis to Donidalorsen for Hereditary Angioedema: 1-Year OASISplus Results. (PubMed, Allergy) - P3 | "In patients who switched from another LTP, donidalorsen was well tolerated and improved long-term HAE attack rates, quality of life, and disease control."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Inflammation • Pruritus

Safety and Efficacy of Donidalorsen in Adolescent Patients With Hereditary Angioedema: 1-Year Results From OASISplus (AAAAI 2026) - P3 | "Methods Patients on stable doses (≥12 weeks) of berotralstat, intravenous (IV) or subcutaneous (SC) C1INH, or lanadelumab switched to donidalorsen 80 mg SC once every 4 weeks without washout per a prespecified algorithm. Findings from 7 additional adolescent patients enrolled in a separate open-label extension cohort of OASISplus were consistent with those reported here. Conclusions In adolescents, donidalorsen had an acceptable safety and tolerability profile and improved HAE attack rates and quality of life, consistent with overall results from OASISplus."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Additional Benefit of Switching to Donidalorsen for Patients with Hereditary Angioedema Having Breakthrough Attacks: Findings from the OASISplus Study (AAAAI 2026) - P3 | "Methods Post-hoc analysis of data from a 52-week study of patients who switched directly from a prior LTP therapy (lanadelumab, C1-INH, or berotralstat) to donidalorsen (OASISplus, NCT05392114, n=64). Conclusions Patients with HAE on LTP therapy who switched to donidalorsen experienced improvements in subjective disease control and QoL regardless of baseline attack rate. Furthermore, patients with a higher baseline breakthrough attack rate reported significantly greater improvements in subjective disease control and QoL."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Association of muscle instability and long-term prophylaxis in hereditary angioedema. (PubMed, World Allergy Organ J) - "CK levels from participants with type 1 or 2 HAE enrolled in the Phase 2 and 3 clinical trials evaluating the safety and efficacy of donidalorsen for LTP in patients with HAE, was measured at baseline (before treatment initiation) and Week 17 (for participants enrolled in Phase 2 Study) and Week 25 (for participants enrolled in Phase 3 study)...The effect of increases in bradykinin in HAE on muscle needs further research but may account for some of the atypical HAE symptoms patients often describe and which are noted in quality-of-life assessments. LTP, therefore, may confer additional benefits beyond reduction of HAE symptoms, potentially contributing to stabilization of skeletal muscle and improvement of fatigue and weakness."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hereditary Angioedema

Donidalorsen for hereditary angioedema: Long-term results from a 4-year phase 2 open-label extension study. (PubMed, Ann Allergy Asthma Immunol) - P2 | "In this 4-year study, donidalorsen led to sustained reductions in monthly HAE attack rate with an acceptable safety profile."

Journal • P2 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

Patient-Reported Disease Control, Work Productivity, and Activity Impairment in Hereditary Angioedema: Insights from OASIS-HAE (AAAAI 2026) - P3 | "Methods Post hoc analyses of the 24-week, Phase 3 OASIS-HAE study (NCT05139810) of donidalorsen versus placebo (n=90, pooled sample) were conducted...Similar findings were observed among patients with complete disease control, but effect sizes were moderate compared to less-than-complete controlled disease (all p<0.05; d=0.57 to 0.76). Conclusions Patients in OASIS-HAE who achieved well- or completely controlled disease experienced significantly fewer impacts on work/school productivity and activities."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

ISIS 721744-CS8: Donidalorsen Treatment in Children with Hereditary Angioedema (clinicaltrialsregister.eu) - P2/3 | N=4 | Not yet recruiting | Sponsor: Ionis Pharmaceuticals Inc.

New P2/3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Donidalorsen for Long-Term Prophylaxis of Hereditary Angioedema Attacks: Results from the OASISplus Open-Label Extension Cohort at Year 1. (PubMed, J Asthma Allergy) - P3 | "Twenty-two (27%) patients reported treatment-related TEAEs; none were serious, and injection-site reactions were the most frequently reported. Donidalorsen demonstrated sustained reductions in HAE attack rate, improvements in QoL, and an acceptable safety profile after 1 year of treatment."

Clinical • Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

The Relationship Between Objective Disease Control at Baseline and Change in Subjective Disease Control and Quality of Life in Patients with Hereditary Angioedema Receiving Donidalorsen (AAAAI 2026) - P3 | "AECT mean change across subgroups was statistically significant in OASISplus (p=0.049 for omnibus ANOVA), but pairwise comparisons were not significant (all p>0.05). Conclusions Findings suggest that patients with HAE who were treated with donidalorsen experienced large improvements in subjective disease control and QoL regardless of baseline HAE attack rate."

Clinical • HEOR • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Predictors of Disease Control, Attack Rate, and Quality of Life in HAE: An Exploratory Analysis (AAAAI 2026) - P3 | "Methods Using OASIS-HAE data, a Phase 3 trial of donidalorsen (NCT05139810, n=90), predictors of change from baseline to Week 24 were assessed via LASSO regression with cross-validated PRESS criterion for 3 outcomes: time-normalized, investigator-confirmed HAE attacks/month; subjective disease control via Angioedema Control Test (AECT, 0-16, higher = better control); and QoL via Angioedema QoL Questionnaire (AE-QoL, 0-100, lower = better QoL)...Other than outcome measure scores, baseline characteristics had limited predictive value. Further research is warranted to identify clinically meaningful predictors of improvement."

HEOR • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

2025 FDA TIDES (Peptides and Oligonucleotides) Harvest. (PubMed, Pharmaceuticals (Basel)) - "Fitusiran and donidalorsen are the first oligonucleotide therapies approved for antithrombin deficiency and hereditary angioedema, respectively, while plozasiran represents the second approved therapy for familial chylomicronemia syndrome...In 2025, elamipretide further expanded this paradigm by becoming the first disease-specific treatment approved for Barth syndrome. This review provides an overview of TIDES approved in 2025, with emphasis on their chemical structures, medical targets, modes of action, routes of administration, and associated adverse effects."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Familial Chylomicronemia Syndrome • Hereditary Angioedema

Population Pharmacokinetic/Pharmacodynamic Modeling of Donidalorsen, an Antisense Oligonucleotide in Development for Prophylaxis of Hereditary Angioedema. (PubMed, CPT Pharmacometrics Syst Pharmacol) - P1, P2a, P3 | "Modeling analyses support that no dose adjustment is needed with respect to intrinsic/extrinsic factors in adults and adolescents with HAE. The nearly identical simulated pharmacokinetic or prekallikrein time courses for Q4W versus monthly dosing and for Q8W versus every-2-month dosing regimens support switching to more convenient regimens for patients."

Clinical • Journal • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

Ionis Pharmaceuticals, Inc…and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced that the European Commission (EC) has approved DAWNZERA (donidalorsen) in the European Union (EU) for the routine prevention of recurrent attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older. (Businesswire) - "The approval follows the positive opinion of the Committee for Medicinal Products for Human Use. The approval is based on positive results from the Phase 3 OASIS-HAE and OASISplus studies, in which DAWNZERA demonstrated positive results across multiple measures of disease including significant and sustained reduction in mean monthly HAE attack rate, with 94% overall mean monthly attack rate reduction at one year in the OASISplus open-label extension study."

EMA approval • Hereditary Angioedema

Association Between the Angioedema Control Test and Attack Frequency in Hereditary Angioedema. (PubMed, Clin Transl Allergy) - P3 | "This study supports the criterion validity of AECT in patients with HAE scores. AECT scores were strongly associated with objective disease control. AECT may be a valuable tool for monitoring disease control in patients with HAE."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pain

Donidalorsen (Dawnzera) for prevention of hereditary angioedema attacks. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Donidalorsen Treatment in Children With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=20 | Not yet recruiting | Sponsor: Ionis Pharmaceuticals, Inc.

New P3 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

Ionis Pharmaceuticals, Inc…announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion of DAWNZERA™ (donidalorsen) for the routine prevention of recurrent attacks of hereditary angioedema (HAE) in adults and adolescents aged 12 years and older. (Businesswire) - "The CHMP opinion was based on positive results from the Phase 3 OASIS-HAE and OASISplus studies...European Commission decision expected in Q1 2026."

CHMP • EMA approval • Hereditary Angioedema

Investigation of the Impact of Hereditary Angioedema (HAE) on Health-Related Quality of Life: A Systematic Literature Review (ISPOR-EU 2025) - "From 100 HRQoL references accepted, 31 were full-text journal articles reporting 27 unique studies that assessed treatment with berotralstat (n=4), C1-INH (n=3), donidalorsen (n=3), garadacimab (n=2), avoralstat, danazol, and lanadelumab (n=1 each); ten included a placebo comparator and twelve were non-interventional studies. Only one study was identified that captured HRQoL during and between patients' HAE attacks. There remains difficulty in accurately quantifying the impact of each attack on HRQoL, likely due to the transient and unpredictable nature of attacks. This highlights the need for further research to improve understanding of how to measure patient HRQoL during attacks."

Clinical • HEOR • Review • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

Matching-Adjusted Indirect Comparison Between Garadacimab and Donidalorsen for Long-Term Prophylaxis in Hereditary Angioedema (ISPOR-EU 2025) - P3 | "These findings demonstrate that garadacimab may provide improved therapeutic benefit compared to donidalorsen for LTP in HAE."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Exposure-Response Analysis of Donidalorsen for the Treatment of Hereditary Angioedema. (PubMed, Clin Transl Sci) - P3 | "Predicted reductions in attack rate remained similar and clinically meaningful in patients who switched from Q1M to Q2M dosing (94.0% in month 1 and 91.3% in month 2 of the 2-month dosing interval at steady state). Overall, exposure-response analyses supported the efficacy of Q1M and Q2M dosing and indicated that switching to Q2M dosing could be a viable approach for patients who are attack-free on the Q1M regimen."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Donidalorsen: First Approval. (PubMed, Drugs) - "Donidalorsen is currently under regulatory review in the EU and in phase III development in several other countries. This article summarizes the key milestones in the development of donidalorsen leading to its first approval for HAE."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Donidalorsen For The Treatment Of Hereditary Angioedema: 1-Year Results From The OASISPlus Open-Label Extension Study (ACAAI 2025) - P3 | "At Week 52, mean HAE attack rate from OASIS-HAE baseline decreased by 94% (Q4W) and 95% (Q8W, Figure ), and patients reported clinically meaningful (≥6-point) improvements in mean AE-QoL total score (Q4W, 28.1 points; Q8W, 26.7 points). Conclusion Donidalorsen demonstrated an acceptable safety profile and improvements in HAE attack rate and QoL at 1-year."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Switching To Donidalorsen For Hereditary Angioedema: 1-Year Results From The Phase 3 OASISplus Study (ACAAI 2025) - P3 | "Methods Patients with HAE on stable doses (≥12 weeks) of lanadelumab, subcutaneous (SC) or intravenous C1 inhibitor (C1INH), or berotralstat switched to 80-mg donidalorsen SC every 4 weeks without washout using a predefined algorithm. Conclusions Donidalorsen was well tolerated by patients switching from prior LTPs. Improvements in HAE attack rate, QoL, and disease control were sustained through 1 year."

P3 data • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Infectious Disease • Respiratory Diseases