Orladeyo (berotralstat) / BioCryst Pharmaceuticals, Royalty, Pint Pharma, Neopharmed - LARVOL DELTA

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

Real-World Attack Rate Reductions After Berotralstat Initiation Among Patients with Hereditary Angioedema with Normal C1-Inhibitor Stratified by Prior Long-Term Prophylaxis (AAAAI 2026) - "Statistically significant monthly attack rate reductions were observed among both LTP-naïve patients (12 months: -3.65; 18 months: -2.75) and LTP-experienced patients (12 months: -1.81; 18 months: -2.24) (all p<0.001). Conclusions Berotralstat was associated with significant real-world attack rate reductions among patients with HAE-nC1INH, regardless of prior LTP treatment history."

Clinical • Real-world • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Reductions in Healthcare Resource Utilization Among Patients with Hereditary Angioedema with C1-Inhibitor Deficiency Following the Initiation of Berotralstat (AAAAI 2026) - "Significant reductions in outpatient/ED visits were observed among all baseline attack-rate subgroups (41%–59%; p<0.05), and in hospitalizations among patients with 2–4 and 0 attacks/month at baseline (81% and 63%; p<0.05). Conclusions Patients with HAE-C1INH had significant reductions in angioedema-related outpatient/ED visits and hospitalizations after the initiation of berotralstat regardless of baseline attack rate."

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

Impact of Berotralstat on Healthcare Resource Utilization in Patients with Hereditary Angioedema with Normal C1-Inhibitor (AAAAI 2026) - "Reductions in visits were observed among all baseline attack-rate subgroups (outpatient/ED visits: 44%–64%, p<0.05; hospitalizations: 17–56%, p=NS). Conclusions Following the initiation of berotralstat, patients with HAE-nC1INH experienced significant reductions in angioedema-related outpatient/ED visits and hospitalizations regardless of their baseline attack rate."

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

Real-world Adherence and Persistence with Long-term Prophylaxis among Patients with Hereditary Angioedema (AAAAI 2026) - "Rationale The treatment landscape for hereditary angioedema (HAE) is evolving rapidly, with several long-term prophylaxes (LTP) approved in the last decade, including Haegarda (subcutaneous injection, every 3-4 days), Takhzyro (subcutaneous injection, every 2-4 weeks) and Orladeyo (once-daily oral capsule). Conclusions These findings suggest suboptimal adherence and persistence to recently approved LTP. Alternative options with a less frequent dosing schedule may help increase adherence and persistence, and could lead to improved outcomes for patients with HAE."

Adherence • Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

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

Oral Berotralstat Reduces the Rate of Moderate and Severe Attacks and Percentage of Days with HAE Symptoms Over 48 Weeks in Children Aged 2 to Less Than 12 Years: Interim Data from APeX-P (AAAAI 2026) - "No patients discontinued due to AEs. Conclusions Pediatric patients experienced reduced HAE burden, with decreased rates of moderate and severe attacks and a reduced percentage of days with HAE symptoms over 48 weeks of treatment, suggesting berotralstat may normalize the lives of pediatric patients with HAE."

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

ASSESSING THE ABILITY OF THE EQ-5D-5L TO CAPTURE LONG-TERM HEALTH-RELATED QUALITY OF LIFE IMPACTS OF HEREDITARY ANGIOEDEMA ATTACKS (ISPOR 2026) - P3 | "This study assessed the ability of the EQ-5D-5L instrument to quantify long-term health-related quality of life (HRQoL) impacts of HAE attacks (beyond and between attacks). We conducted a secondary analysis of APeX-2 (NCT03485911), a phase 3 trial of berotralstat for long-term prophylaxis in HAE... This study showed weak associations between HAE attack characteristics and EQ-5D-5L index scores. The EQ-5D-5L appears unable to capture the longer-term (between attack) HRQoL impacts of HAE. Likely contributing factors are the generic nature of the EQ-5D-5L being insensitive to HRQoL changes in HAE, and the short reference period ('health today') of the EQ-5D-5L, which is not optimal when HAE attacks occur sporadically and/or infrequently."

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

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

Impact of Berotralstat on Hereditary Angioedema Attack Rates in Patients with C1-Inhibitor Deficiency: Real-World Evidence Stratified by Prior Long-Term Prophylaxis (AAAAI 2026) - "Monthly attack rates significantly decreased at 12 and 18 months by -1.97 and -2.19 per patient among LTP-naïve, and by -1.32 and -1.59 per patient among LTP-experienced patients (all p<0.001). Conclusions Among patients with HAE-C1INH, berotralstat was associated with significant HAE attack rate reductions in the real world regardless of prior LTP treatment history."

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Medication Routines Among Patients With Hereditary Angioedema (AAAAI 2026) - "Patients found that berotralstat fit easily into their daily routine. The administration convenience of berotralstat positively impacted medication adherence."

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

Utility of fluorescamine for spectrofluorimetric quantitation of berotralstat hydrochloride in spiked human plasma and content uniformity test and evaluation of method greenness. (PubMed, Sci Rep) - "Additionally, it was applied to examine the content uniformity in accordance with US Pharmacopeia requirements. Furthermore, the results of the ecology scale scores indicated that the analytical process involved was green."

Journal

Attack rate reductions following berotralstat initiation among US patients with hereditary angioedema in the real-world. (PubMed, Allergy Asthma Clin Immunol) - "Berotralstat was associated with significant and sustained reductions in attack rates among patients with HAE, regardless of baseline attack rate. Patients with 0 baseline attacks/month maintained low attack rates following berotralstat initiation."

Journal • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases

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

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

APeX-A: Open-label Berotralstat Access to HAE Patients Previously Enrolled in Berotralstat Studies (clinicaltrials.gov) - P3 | N=139 | Enrolling by invitation | Sponsor: BioCryst Pharmaceuticals | Active, not recruiting ➔ Enrolling by invitation

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

Comparative efficacy and safety of FDA-approved prophylactic treatments for hereditary angioedema, including garadacimab, haegarda, lanadelumab, and berotralstat: A network meta-analysis (ASH 2025) - "This network meta-analysis offers a detailed comparison of the efficacy and safety profiles ofFDA-approved prophylactic treatments for HAE. Garadacimab emerged as the most effective treatment,followed by Haegarda, Lanadelumab, and Berotralstat. These findings emphasize the importance ofevaluating both efficacy and safety when selecting the optimal treatment for HAE patients, withsignificant improvements in quality of life observed in the treatment group."

Retrospective data • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema • Novel Coronavirus Disease

BioCryst Announces FDA Approval of ORLADEYO (berotralstat) Oral Pellets, First and Only Oral Prophylactic Treatment for Patients with HAE Aged 2 to <12 Years (GlobeNewswire) - "This approval was supported by positive interim data from the APeX-P clinical trial, the largest trial to date evaluating a long-term prophylactic therapy for HAE in patients 2 to <12 years of age."

FDA approval • Hereditary Angioedema

Hereditary Angioedema Prophylaxis Therapy: Berotralstat and Lanadelumab Safety Profile. (PubMed, Medicina (Kaunas)) - " The results confirmed the literature's data on the gastrointestinal adverse effects of berotralstat, as well as site reactions and infections associated with lanadelumab. Notably, musculoskeletal and connective tissue disorders, immune system disorders, vascular disorders, and metabolic issues occurred more frequently in patients using lanadelumab."

Journal • Retrospective data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Infectious Disease • Musculoskeletal Diseases • Rheumatology

Berotralstat, the first oral prophylaxis for hereditary angioedema in children aged 2 to 12 years: The kids are alright! (PubMed, Ann Allergy Asthma Immunol) - No abstract available

Journal • Cardiovascular • Complement-mediated Rare Disorders • 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

Linking Specialty Pharmacy Data With Healthcare Claims Data in a Rare Disease: Comprehensively Characterizing Patients With Hereditary Angioedema Treated With Berotralstat (ISPOR-EU 2025) - "The innovative linking of Optime Care Specialty Pharmacy and Komodo Healthcare Map data allows for comprehensive characterization of patients with HAE treated with berotralstat. The linked database enables future research in a rare disease to address knowledge gaps and support decision-making by healthcare practitioners and payers."

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

Hereditary Angioedema Attack Rates In Children 2–12 With Oral Prophylactic Berotralstat Over One Year (ACAAI 2025) - "No drug-related Grade 3/4 or serious TEAEs, deaths, or discontinuations related to TEAEs occurred. Conclusion In APeX-P, the largest trial of LTP in pediatric patients aged 2 to <12 years with HAE, berotralstat was well-tolerated and led to early and sustained reductions in monthly attack rates over one year."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Infectious Disease • Pediatrics • Respiratory Diseases

Berotralstat Is Effective In Early Onset HAE With Normal C1 Esterase Inhibitor (ACAAI 2025) - "Previously failed treatments included C1 esterase inhibitor, lanadelumab-flyo, progestin, and omalizumab, which were either ineffective or caused significant side effects. She required icatibant injections for acute attacks due to the severity of symptoms...In one case series that demonstrated the effectiveness of berotralstat in this condition, most patients had adult-onset presentations (average age of onset for these patients was 32 years), whereas only 2 out of the 15 patients had childhood-onset presentations (ages unreported). Our case demonstrates the effectiveness of berotralstat in early onset HAE-nC1-INH."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

A Case of HAE-ANGPT1 Treated with berotralstat - Insights into Pathophysiology (ACAAI 2025) - "Although some patients with ANGPT1 mutations have responded to icatibant—a bradykinin B2 receptor antagonist—the role of bradykinin-generating pathways, such as the contact activation system, remains poorly understood. While ANGPT1 mutations are thought to act via endothelial dysfunction, this response suggests a role for the kallikrein-kinin system. These findings support further exploration of contact pathway inhibitors in managing this HAE subtype."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Immunology • Otorhinolaryngology • Pulmonary Disease • Urticaria • ANGPT1

Type I Hereditary vs Acquired Angioedema Onset in Older Adulthood (ACAAI 2025) - "She responded well to prophylaxis with oral kallikrein inhibitor (berotralstat), which is common in HAE versus AAE which benefits most from treatment of underlying cause. Our case highlights the overlapping features between HAE and AAE, which may lead to decreased recognition of AAE."

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