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

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

Impact of Donidalorsen In Patients With Hereditary Angioedema By Baseline Attack Rate From OASISplus (ACAAI 2025) - P3 | "No safety signals were identified in OLE patients within the first year. Conclusion In this post hoc analysis, donidalorsen improved HAE attack rates by 90–95% regardless of baseline attack rate and provided an attack-free period for a substantial percentage of subjects."

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

Phase 2 Open-Label Extension Study Of Donidalorsen In Patients With Hereditary Angioedema: A 4-Year Analysis (ACAAI 2025) - P2, P2a | "The median longest attack-free duration was 990 days; 71% of patients were attack-free for >1 year. Conclusion Donidalorsen treatment led to sustained reductions in HAE attacks and had an acceptable safety profile during the 4-year study, including those who switched from Q4W to Q8W dosing."

Clinical • P2 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Garadacimab (Andembry) for hereditary angioedema prophylaxis. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Donidalorsen Treatment of Hereditary Angioedema in Patients Previously on Long-Term Prophylaxis. (PubMed, J Allergy Clin Immunol Pract) - P3 | "Donidalorsen was well tolerated, decreased HAE attack rate, and improved QoL and disease control. Most patients preferred donidalorsen over their prior treatment. Further analyses are planned at week 52."

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

Donidalorsen Shows Promise Reducing HAE Attacks Ahead of August PDUFA (HCPLive) - P3 | N=154 | OASISplus (NCT05392114) | Sponsor: Ionis Pharmaceuticals, Inc | "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. Ionis Pharmaceuticals announced this promising pivotal data...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...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."

P3 data • PDUFA • Hereditary Angioedema

Ionis reports second quarter 2025 financial results and highlights progress on key programs (Businesswire) - "TRYNGOLZA (olezarsen): Generated net product sales of $19 million in the second quarter of 2025, its second full quarter on the market, and $26 million in the first half of 2025...Olezarsen on track for topline Phase 3 data from pivotal CORE and CORE2 studies in patients with sHTG in September 2025, positioning olezarsen to potentially treat this second, more prevalent patient population with high unmet need....Donidalorsen on track to launch this year, assuming approval, with a U.S. PDUFA date of August 21, 2025. Poised to transform the treatment paradigm for individuals with hereditary angioedema (HAE) as the first and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector monthly or every other month."

Launch US • P3 data: top line • PDUFA • Sales • Familial Chylomicronemia Syndrome • Hereditary Angioedema • Severe Hypertriglyceridemia

A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE) (clinicaltrials.gov) - P3 | N=154 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Ionis Pharmaceuticals targets $750M revenue for 2025 with multiple launches underway (MSN News) - "The company is preparing for several upcoming launches, including donidalorsen for hereditary angioedema (HAE) in Q3 2025 and olezarsen for severe hypertriglyceridemia (sHTG) next year, positioning Ionis for substantial growth....The company plans to submit a supplemental New Drug Application (sNDA) for olezarsen by year-end, following Phase III data from CORE and CORE2 studies expected in Q3 2025."

FDA filing • Launch • P3 data • Hereditary Angioedema • Severe Hypertriglyceridemia

Patient-Reported Outcomes in the Phase III OASIS-HAE Study of Donidalorsen for Hereditary Angioedema. (PubMed, Allergy) - P3 | "Donidalorsen significantly improved QoL and other PROs vs. placebo in patients with HAE."

Journal • P3 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

An Extension Study of Donidalorsen (IONIS-PKK-LRx) in Participants With Hereditary Angioedema (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

New positive donidalorsen data to be presented at AAAAI/WAO Joint Congress highlight sustained HAE attack rate reduction and disease control (Businesswire) - "Ionis Pharmaceuticals, Inc...today announced that it will present additional data from the pivotal Phase 3 OASIS and OASISplus studies, as well as three year data from the Phase 2 open-label extension (OLE) study of donidalorsen, the company’s investigational RNA-targeted prophylactic medicine for hereditary angioedema (HAE). Results will be presented at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI) / World Allergy Organization (WAO) Joint Congress in San Diego, California...'In new analyses from our OASISplus prospective switch cohort, donidalorsen continued to demonstrate the ability to reduce the HAE attack rate burden and improve quality of life in patients previously on other prophylactic treatments, with the simplicity of monthly or every two-month self-administration via an autoinjector.'"

P2 data • P3 data • Hereditary Angioedema

Ionis reports fourth quarter and full year 2024 financial results (Businesswire) - "'Over the next three years, we expect three more independent launches, including donidalorsen later this year for hereditary angioedema and olezarsen for severe hypertriglyceridemia in 2026, pending Phase 3 results in the second half of this year. Additionally, our partners are on track to launch four Ionis-discovered medicines over the same time period, including several that address broad patient populations'...WAINUA...Generated sales of $85 million resulting in royalty revenue of $20 million in the year ended December 31, 2024...SPINRAZA...generated global sales of $1.6 billion resulting in royalty revenue of $216 million in year ended December 31, 2024...Higher dose nusinersen under regulatory review in U.S. (PDUFA date of September 22, 2025) and EU. QALSODY (tofersen) for the treatment of SOD1-ALS generated global sales of $32 million resulting in royalty revenue of $4 million in the year ended December 31, 2024."

Launch • P3 data • PDUFA • Sales • Amyloidosis • Amyotrophic Lateral Sclerosis • Cardiovascular • Genetic Disorders • Hereditary Angioedema • Muscular Atrophy • Severe Hypertriglyceridemia

Efficacy And Safety Of Donidalorsen In Adolescent Patients With Hereditary Angioedema: A Subanalysis Of The Phase 3 OASIS-HAE Study (AAAAI-WAO 2025) - P3 | "Three patients had treatment-emergent adverse events (Q4W, n=2; Q8W, n=1), 2 of which were non-treatment-related, and none of which were serious or led to treatment discontinuation. Conclusions Donidalorsen improved HAE attack rates, quality of life, and disease control in adolescents and was well-tolerated, consistent with overall results from OASIS-HAE."

Clinical • P3 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Correlation Between Subjective And Objective Disease Control In Hereditary Angioedema: Association Between The Angioedema Control Test And Attack Rate (AAAAI-WAO 2025) - P3 | "Methods In the phase 3, double-blind, placebo-controlled OASIS-HAE study (NCT05139810), patients with HAE were randomized to donidalorsen 80 mg or placebo subcutaneously over 24 weeks...At Week 24, 37 of 38 (97.4%) patients reporting complete control (AECT=16) had an attack rate of 0, while patients with an attack rate of 0 over the previous month had mean AECT=15.1 vs. 7.7 for patients with attack rate >0. Conclusions Results support strong concordance between subjective (AECT) and objective (attack rate) disease control in patients with HAE."

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

Hereditary Angioedema Disease Control After Switching To Donidalorsen From Prior Long-Term Prophylaxis: Results From The OASISplus Open-Label Extension Study (AAAAI-WAO 2025) - P3 | "In patients reporting poorly-controlled disease at baseline, mean monthly HAE attack rates decreased by 73% (lanadelumab), 60% (C1INH), and 76% (berotralstat). Conclusions Switching from lanadelumab, C1INH, or berotralstat to donidalorsen improved patient-reported disease control and reduced HAE attack rates."

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

Participant Reported Ease-of-Use with a Prefilled, Single-dose, Disposable Autoinjector for the Treatment of Hereditary Angioedema (AAAAI-WAO 2025) - "The autoinjector is a surrogate version of the ones used in the investigational donidalorsen clinical studies...88% (100/114) of participants successfully administered a full dose of surrogate into an injection cushion while following the IFU without further instruction from the study moderator. Conclusions This study indicated that the disposable autoinjector being developed for use in patients with HAE was easy to use with ∼90% of participants able to successfully administer a dose."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Patient-Reported Injection-Site Pain And Treatment Satisfaction After Switching From Long-Term Prophylaxis To Donidalorsen For The Treatment Of Hereditary Angioedema: Results From The OASISplus Study (AAAAI-WAO 2025) - P3 | "Global treatment satisfaction (TSQM-II) scores increased (i.e., improved satisfaction) from baseline to Week 16: berotralstat (50.9) to donidalorsen (92.5), C1INH (76.1) to donidalorsen (88.4), and lanadelumab (84.3) to donidalorsen (88.6); effectiveness and convenience domains also improved from baseline to Week 16. Conclusions Patient-reported ISP and treatment satisfaction improved after switching from prior LTPs to donidalorsen."

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

Long-Term Analysis of the Phase 2 Open-Label Extension of Donidalorsen in Patients With Hereditary Angioedema (AAAAI-WAO 2025) - P2, P2a | "In patients with available data at the prespecified Week 157 timepoint (n=12), the mean Angioedema-Quality of Life (AE-QoL) total score decreased in the Q4W and Q8W groups by 21 points (n=7; functioning, 31; fatigue/mood, 12; fear/shame, 22; nutrition, 20) and 22 points (n=5; functioning, 38; fatigue/mood, 15; fear/shame, 17; nutrition, 21), respectively. Conclusions At the Week 197 data cutoff, donidalorsen was well-tolerated, led to sustained reductions in HAE attacks, and improved QoL."

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