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

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

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

Prolonged QT Syndrome Complicated By Cardiac Arrest: Did Berotralstat Play A Role? (ACAAI 2025) - "Berotralstat was discontinued in favor of lanadelumab-flyo. In this case, there were numerous complications of hypomagnesemia, hypokalemia, and use of haloperidol (metabolized by CYP2D6 and CYP3A4) that resulted in prolongation of QT interval, Torsade’s de pointes, and ultimately cardiac arrest. Prior to starting Berotralstat as HAE prophylaxis, patients should be evaluated for prolonged QT, advised to avoid QT prolonging medications, and advised to avoid medications metabolized by CYP2D6 or CYD3A4."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Ventricular Tachycardia • Women's Health • CYP3A4

Real-world Impact of Long-term Prophylaxis on the Clinical Burden of Patients with Hereditary Angioedema (ACAAI 2025) - "Results A total of 499 patients were included (57 Haegarda [11%], 257 Orladeyo [52%], 185 Takhzyro [37%]) and followed for 11.3 months on average. In these 449 patients, annual HRU remained substantial before and after LTP initiation across settings (inpatient days: 2.4 and 1.7 days [0.3 and 0.2 admissions]; ED: 1.5 and 1.2 admissions; outpatient: 21.0 and 19.3 visits, respectively; Figure ). Conclusion This real-world study suggests that currently available LTP can partly reduce the clinical burden of patients with HAE but need remains for novel therapies that may further alleviate this burden."

Clinical • Real-world • Real-world evidence • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Metabolic Disorders • Obesity • Pulmonary Disease • Respiratory Diseases

Non-CME Corporate Forum - BioCryst Pharmaceuticals, Inc : Conversations in Care: Engaging Clinical Experts on Real-World Experience of ORLADEYO® (berotralstat) (ACAAI 2025) - "Also visit BioCryst Pharmaceuticals, Inc. at Booth #501 ."

Clinical • Real-world • Real-world evidence

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

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

Hereditary Angioedema With Normal C1 Esterase Inhibitor: A Case of a Late Diagnosis in a 48-Year-Old Male. (PubMed, Cureus) - "Prior treatments, including corticosteroid injections and oral prednisone, were ineffective...The patient was prescribed icatibant for acute flares and berotralstat for prophylaxis...Increased awareness of HAE-nC1-INH among clinicians is essential to improve timely diagnosis and appropriate treatment. This case underscores the importance of differentiating HAE-nC1-INH from other forms of angioedema to prevent misdiagnosis."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Dyslipidemia • Epstein-Barr Virus Infections • Hereditary Angioedema • Immunology • Rare Diseases

Berotralstat effectiveness and safety in patients with hereditary angioedema with normal C1 inhibitor. (PubMed, J Allergy Clin Immunol Glob) - "Long-term prophylactic berotralstat was effective in reducing HAE attacks for 5 of 6 patients with HAE-nC1-INH. No significant safety signals were noted."

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

LATE-ONSET HEREDITARY ANGIOEDEMA DUE TO PLASMINOGEN MUTATION: A RARE PRESENTATION REQUIRING INTUBATION (CHEST 2025) - "These episodes were reported to have slowly resolved with oral diphenhydramine and were unassociated with hives...On arrival to the ED, the patient was treated with intramuscular epinephrine, methylprednisolone, and tranexamic acid...After two days of mechanical ventilation, he was successfully extubated and continued on methylprednisolone, cetirizine, famotidine, and hydroxychloroquine...For long-term prophylaxis, the patient was started on berotralstat (a plasma kallikrein inhibitor)...He has done well with this plan, with minimal breakthrough attacks of mild severity and excellent response to icatibant when used... Although literature on HAE-nl-C1-INH remains limited, current management includes on-demand treatment of acute attacks regardless of location or severity, long-term prophylaxis, and short-term prophylaxis before medical procedures or stressful life events."

Intubation • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Mood Disorders • Rosacea • Urticaria • ANGPT1

National Audit of Long-Term Real-World Outcomes of Berotralstat Use in UK Patients With Hereditary Angioedema. (PubMed, Allergy) - No abstract available

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

Perioperative Management of NSTEMI and CABG in a Patient with Hereditary Angioedema: A Case for Interdisciplinary Care (ASA 2025) - "Given the high risk of acute angioedema, perioperative HAE prophylaxis included berotralstat, icatibant, and plasma-derived C1-inhibitor concentrate. An interdisciplinary team consisting of Allergy/Immunology, Anesthesiology, Cardiothoracic Surgery, and perfusion collaborated closely to minimize the risk of edema and maintain hemodynamic stability. This case highlights the complexities of managing rare comorbidities in high-risk cardiac surgery and underscores the importance of proactive, coordinated care to mitigate perioperative complications and optimize outcomes."

Clinical • Anesthesia • Cardiovascular • Complement-mediated Rare Disorders • Coronary Artery Disease • Hereditary Angioedema • Immunology

Perioperative Management of Hereditary Angioedema in a High-Risk Patient Undergoing Glioma Biopsy (ASA 2025) - "The patient was taking Orladeyo and Firazyr, but he continued to experience severe edema exacerbated by daily stressors (e.g. gardening), which was concerning for perioperative airway management. We administered prophylactic C1 esterase inhibitor and total intravenous anesthetic with propofol and dexmedetomidine to facilitate smooth induction and emergence. Rapid sequence intubation with video laryngoscope was performed to secure the airway quickly with minimal trauma. Multimodal analgesia, maintenance of homeostasis, extubation over exchange catheter, and post-operative airway monitoring in ICU contributed to a successful perioperative management of HAE."

Biopsy • Clinical • Anesthesia • Brain Cancer • Cardiovascular • Complement-mediated Rare Disorders • Glioma • Hereditary Angioedema • Mood Disorders • Solid Tumor

Absolute Configuration of Key Intermediates and the Gram Scale Synthesis of Berotralstat and ent-Berotralstat. (PubMed, J Org Chem) - "Key intermediates were isolated, and their stereochemistry confirmed via X-ray diffraction. These efforts enabled the scalable preparation of 16 g of berotralstat in 61% yield and nearly 1 g of its enantiomer in 23% yield─representing the first reported gram-scale synthesis of both compounds."

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

BioCryst Pharmaceuticals, Inc…announced that it has successfully completed the previously announced sale of its European ORLADEYO business to Neopharmed Gentili. (BioCryst Press Release) - "BioCryst received $250 million upfront for the European assets and rights related to ORLADEYO (subject to customary purchase price adjustments) and may receive up to $14 million in future milestones associated with sales in Central and Eastern Europe."

Commercial • 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

Oral berotralstat for hereditary angioedema prophylaxis in patients aged 2 to <12 years: APeX-P interim results. (PubMed, Ann Allergy Asthma Immunol) - P3 | "Oral berotralstat was well tolerated and resulted in early and sustained reductions in HAE attack rates."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema • Infectious Disease • Pain • Pediatrics • Respiratory Diseases