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

Current and future therapies for bradykinin-mediated angioedema (PubMed, Dermatologie (Heidelb)) - "On-demand treatment options include plasma-derived and recombinant C1 inhibitor (C1INH) concentrates, the bradykinin B2 receptor antagonist icatibant, and, more recently, the first orally available plasma kallikrein inhibitor, sebetralstat...LTP therapies include subcutaneous and intravenous C1INH preparations, the oral kallikrein inhibitor berotralstat, the anti-kallikrein monoclonal antibody lanadelumab, the factor XIIa inhibitor garadacimab, and the antisense oligonucleotide donidalorsen. Currently under development are the oral bradykinin B2 receptor antagonist deucrictibant, which is intended for both on-demand treatment and long-term prophylaxis in different formulations, long-acting antibodies, such as navenibart, and CRISPR/Cas9-based gene-editing therapies, such as NTLA-2002 with potential functional curative properties. In particular, orally available and long-acting therapies are expected to improve adherence, self-management, and quality of life in..."

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

Donidalorsen for the Treatment of Hereditary Angioedema: A Review of Clinical Studies. (PubMed, Drug Des Devel Ther) - "A notable study in the clinical program included a cohort of patients who switched from berotralstat, C1 inhibitor, or lanadelumab to donidalorsen for up to 1 year; mean attack rates were reduced by 68% vs baseline (on prior HAE prophylaxis). Across studies, donidalorsen had an acceptable safety and tolerability profile, with mostly mild to moderate adverse events reported. Overall, the clinical data are promising for donidalorsen as a long-term prophylactic medication for HAE."

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

Psychometric validation of the Angioedema Quality of Life Questionnaire (AE-QoL) for hereditary angioedema. (PubMed, J Patient Rep Outcomes) - P3 | "The AE-QoL demonstrated strong reliability, validity, and ability to detect change, supporting its use as an important patient-reported outcome measure for evaluating HRQoL in patients with HAE."

Clinical • HEOR • Journal • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hereditary Angioedema • Rare Diseases

The Medicines and Healthcare products Regulatory Agency (MHRA) has today, 7 May 2026, approved donidalorsen (Dawnzera) for use in patients 12 years and older with hereditary angioedema (HAE) to prevent angioedema attacks. (GOV.UK) - "In a main study, donidalorsen significantly reduced the number of attacks in people with hereditary angioedema compared with placebo. The main study involved 91 patients from 12 years of age with hereditary angioedema. The patients received donidalorsen either every 4 weeks or every 8 weeks, or placebo."

MHRA approval • Genetic Disorders

DAWNZERA (donidalorsen), the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in patients 12 years of age and older (Businesswire) - "Generated U.S. net product sales of $16 million in the first quarter of 2026, an increase of 125% versus the fourth quarter of 2025; Launch initiated in the EU by Otsuka"

Launch Europe • Sales • Hereditary Angioedema

Status of Current Clinical Trials on Therapy for Hereditary Angioedema (IMMUNOLOGY 2026) - "The sole drug in phase 4 is CSL312 (Garadacimab), a fully human IgG4 monoclonal antibody targeting activated factor XIIa. Drugs in phase 3 include: NTLA-2002, a single-dose intravenous gene therapy targeting inactivation of the KLKB1 gene; Navenibart, an IgG1 monoclonal antibody inhibiting activated kallikrein; OCTA-C1-INH, a virus-inactivated, nanofiltrated, highly purified concentrate of C1-INH derived from pooled human plasma; ADX-324, an siRNA therapy to reduce hepatic production of prekallikrein (PKK); Donidalorsen, an antisense oligonucleotide targeted against hepatic PKK mRNA; Sebetralstat and berotralstat, both plasma kallikrein inhibitors that reduce production of bradykinin; and deucrictibant, a competitive bradykinin B2 receptor antagonist. Advances in gene therapy, biologics, RNA interference therapeutics, and improved replacement strategies hold promise for transforming both rescue and prophylactic management for HAE. Ongoing evaluation of safety,..."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema • AVEN

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