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

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

Clinical presentation and management of 239 children and adolescents with hereditary angioedema. (PubMed, J Allergy Clin Immunol Pract) - No abstract available

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

Comment on: "A national survey of four decades of hereditary angioedema prophylaxis" - The emerging role of Garadacimab. (PubMed, Clin Immunol) - No abstract available

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

FDA extends review period for BioCryst pediatric drug application to December (Investing.com) - "The U.S. Food and Drug Administration has extended its review period for BioCryst Pharmaceuticals’...new drug application for once-daily ORLADEYO (berotralstat) oral granules intended for pediatric patients with hereditary angioedema aged 2 to 11 years. The company reported Monday that the FDA determined additional final reports and formulation data submitted by BioCryst represented a major amendment to the application, which resulted in a standard three-month extension of the Prescription Drug User Fee Act (PDUFA) goal date. The new target action date for the FDA’s decision is December 12, 2025. The original review timeline was extended to allow the agency sufficient time to complete a full evaluation of the new information provided."

PDUFA • Hereditary Angioedema

Hereditary angioedema treatment beyond biologics: current state of preventive and on-demand approaches and new perspectives. (PubMed, Expert Opin Pharmacother) - "Accordingly, a new era toward oral formulations has begun starting from berotralstat, with a consistent number of drugs under development...Oral treatment could address practical needs for HAE patients both in preventive and on-demand setting, avoiding injection-related side effects, reducing treatment burden, and improving quality of life. In the next future, significant advances in HAE therapeutics could result from gene therapy."

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

A national survey of four decades of hereditary angioedema prophylaxis: Efficacy and safety of old and new drugs. (PubMed, Clin Immunol) - "Modern prophylaxis usage is increasing among Hungarian HAE-C1INH patients, following the global trends. Both modern and traditional LTP options proved safe and effective in our patient population when used with appropriate monitoring."

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

Long-term safety and efficacy of once-daily berotralstat in patients with hereditary angioedema: APeX-S final results. (PubMed, Ann Allergy Asthma Immunol) - P2/3 | "This study supports the long-term safety of berotralstat and its efficacy at preventing HAE attacks and improving QoL."

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

ORLADEYO (berotralstat) Approved in Colombia (GlobeNewswire) - "BioCryst Pharmaceuticals, Inc...today announced that the National Institute of Drug and Food Surveillance (INVIMA) in Colombia has granted approval for oral, once-daily ORLADEYO (berotralstat) for the prophylaxis of hereditary angioedema (HAE) attacks in adults and pediatric patients 12 years of age or older."

Approval • Hereditary Angioedema

Navigating anaesthetic challenges of C1 esterase inhibitor type 1 patient during emergency dental extraction under conscious sedation: a case report (Euroanaesthesia 2025) - "His HAE was diagnosed at age 8, with previous management including tranexamic acid and icatibant. He subsequently transitioned to Berotralstat, though adherence to scheduled appointments remained challenging due to needle phobia...Conscious sedation (midazolam, fentanyl, propofol) and local anaesthesia facilitated the uneventful extraction...Further research is warranted to optimize management protocols for such scenarios.Learning points: Successful perioperative management of hereditary angioedema (HAE) requires a multidisciplinary approach incorporating prophylactic C1-INH to prevent acute attacks, conscious sedation to minimize airway risk, and individualized care plans addressing patient-specific factors such as needle phobia. Patient education is critical for treatment adherence and optimal outcomes."

Case report • Clinical • Anesthesia • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Rare Diseases • CRP

Reductions in medical visits and hospitalizations following berotralstat initiation in patients with hereditary angioedema in the United States. (PubMed, J Manag Care Spec Pharm) - "Results were similar among subgroups of patients defined by HAE treatment history, including patients who were LTP-experienced (n = 126) and LTP-naive but on-demand treatment-experienced (n = 67). Prophylactic treatment of HAE with berotralstat was associated with significant reductions in all-cause HRU, including decreases to angioedema-related and HAE attack-related medical visits, hospitalizations, and administration of on-demand treatment."

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

Network Meta-Analysis of Pharmacological Therapies for Long-Term Prophylactic Treatment of Patients with Hereditary Angioedema. (PubMed, Drugs R D) - "Overall, garadacimab ranked as the most probable effective treatment among all comparators assessed, with lanadelumab Q2W or subcutaneous C1INH ranking second, across most outcomes."

Journal • Retrospective data • 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 | Active, not recruiting | Sponsor: BioCryst Pharmaceuticals | Trial completion date: Aug 2026 ➔ Aug 2031 | Trial primary completion date: Aug 2026 ➔ Aug 2031

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

Real-World Hereditary Angioedema Attack Rates Before and After Berotralstat Initiation Among Patients With C1 Inhibitor Deficiency (Type I/II) and =8 Attacks Per Month (ISPOR 2025) - "Patients with ≥8 monthly baseline attacks and C1-inhibitor deficiency reported significantly lower HAE attack rates after berotralstat initiation. Treatment effectiveness was consistent and sustained through 18 months of follow-up."

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

Real-World Hereditary Angioedema Attack Rates Before and After Berotralstat Initiation Among Adolescents (ISPOR 2025) - "Adolescents initiating berotralstat reported statistically significant and sustained reductions in HAE attack rates through 18 months of follow-up."

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

Assessment of potential drug-drug interactions in patients with hereditary angioedema from the ITACA cohort: simulations from a real-life dataset considering danazol versus berotralstat. (PubMed, Front Pharmacol) - "The second checker identified, respectively, 66 and 14 DDIs for Danazol (20% severe, regarding Simvastatin and Rivaroxaban) and Berotralstat (0% severe). Berotralstat was consistently associated with a reduced risk of DDIs compared with Danazol. A rational assessment of DDIs would help select the best prophylactic treatment for HAE."

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

BioCryst Announces FDA Acceptance of NDA for ORLADEYO (berotralstat) Oral Granules in Patients with Hereditary Angioedema Aged 2 to 11 Years (GlobeNewswire) - "BioCryst Pharmaceuticals, Inc...announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for the use of oral, once-daily ORLADEYO (berotralstat) in pediatric patients with hereditary angioedema (HAE) aged 2 to 11 years. The FDA also granted Priority Review of the application, with a Prescription Drug User Fee Act (PDUFA) target action date of September 12, 2025....The NDA was based on positive interim data from the APeX-P clinical trial, the largest trial evaluating a prophylactic therapy for HAE in patients 2 to 11 years of age."

FDA filing • PDUFA • Priority review • Hereditary Angioedema

BioCryst Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "ORLADEYO net revenue in the first quarter of 2025 was $134.2 million (+51 percent year-over-year (y-o-y)). The total percentage of all ORLADEYO patients on paid drug has increased to approximately 84 percent (compared to 73.5 percent at end of 2024), generating higher than expected ORLADEYO revenue that the company expects will continue through the full year....Sales from the U.S. contributed 89.5 percent of global ORLADEYO net revenues in the first quarter. The number of patients treated with ORLADEYO outside the U.S. continued to grow in new and existing markets....The company has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) to expand the ORLADEYO label to children with HAE aged 2 to 11 using an oral granule formulation. The company also expects to submit regulatory filings in 2025 in global territories, including Europe, Japan and Canada."

Canada filing • EMA filing • FDA filing • Japan filing • Sales • Hereditary Angioedema

Adherence and persistence among patients with hereditary angioedema receiving long-term prophylaxis in the United States. (PubMed, Allergy Asthma Proc) - "Adherence and persistence rates for all three LTP treatments were uniformly high. Berotralstat adherence andpersistence were comparable with those observed after lanadelumab or SC-pdC1-INH initiation in the main analysis, among patients with two or more claims for their index LTP, and among cohorts assigned based on the first claim for qualifying LTP."

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

Transitioning from nonspecific therapy to berotralstat in hereditary angioedema type I: real world data from three patients within the same family. (PubMed, Eur Ann Allergy Clin Immunol) - No abstract available

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

BioCryst Reports Fourth Quarter and Full Year 2024 Financial Results and Upcoming Key Milestones (GlobeNewswire) - "ORLADEYO net revenue in the fourth quarter of 2024 was $124.2 million (+36.6 percent y-o-y). 73.5 percent of U.S. patients were on paid product at the end of the fourth quarter (up from 71.4 percent at the end of 2023). Sales from outside the U.S. contributed 13.9 percent of global ORLADEYO net revenues in the fourth quarter and 11.8 percent for full year 2024...ORLADEYO is now reimbursed in all major countries in Western Europe, except the Netherlands, which is expected in 1H 2025...The company has advanced BCX17725, its KLK5 inhibitor for the treatment of Netherton syndrome, into clinical trials and expects initial data from the program in 2025...In 2025, the company plans to advance avoralstat, a plasma kallikrein inhibitor, into a clinical trial of patients with diabetic macular edema (DME)."

Commercial • New trial • P1 data • Reimbursement • Diabetic Macular Edema • Genetic Disorders • Hereditary Angioedema • Rare Diseases

BioCryst Announces Positive Results from APeX-P Trial for ORLADEYO (berotralstat) in Pediatric Patients with Hereditary Angioedema Aged 2 to <12 Years (GlobeNewswire) - P3 | N=29 | APeX-P (NCT05453968) | Sponsor: BioCryst Pharmaceuticals | "We remain on track to submit our New Drug Application to the FDA this year...ORLADEYO was safe and well tolerated in APeX-P, with no new safety signals identified. Adverse events (AEs) were similar across all ages and weights. ORLADEYO resulted in early and sustained reductions in monthly attack rates. The median (range) and mean (±SEM) monthly attack rates in the standard-of-care period were 0.96 (0–5.0) and 1.5 (±0.2) attacks/month, respectively. After one month of taking ORLADEYO, median and mean monthly attack rates dropped to 0 (0-4.0) and 0.5 (±0.2), and the median monthly attack rate remained at 0 through month 12 (month 12 range: 0-1.7); the mean monthly attack rate at month 12 was 0.3 (±0.1). Eighty-three percent of participants experienced symptom onset before six years of age and 90 percent were diagnosed with HAE in the same timeframe."

FDA filing • P3 data • Hereditary Angioedema

Patient-Reported Impact of Berotralstat as Long-Term Prophylaxis on Hereditary Angioedema Attack Frequency and Attack Severity (GlobeNewswire) - "U.S. patients with HAE (n=124) who had been treated with ORLADEYO participated in an online discussion and survey about their experiences with ORLADEYO and other HAE therapies; participants had a mean age of 43.2, a mean of 13.4 years since diagnosis and 54 percent had been on ORLADEYO for at least one year. Most participants, including those switching from prior LTP and those who had been on ORLADEYO for less than one year, reported having less frequent and less severe attacks after starting ORLADEYO. All participants were either 'extremely satisfied' or 'somewhat satisfied' with their initiation of, or transition to, ORLADEYO with respect to HAE attack frequency and severity."

Real-world • Hereditary Angioedema

Real-World Attack Rates Before and After Berotralstat Initiation Among Patients with Hereditary Angioedema without C1-Inhibitor Deficiency (HAE-nl-C1-INH) Stratified by Monthly Baseline HAE Attack Frequency (GlobeNewswire) - "Patients with HAE-nl-C1-INH (n=353) experienced statistically significant, sustained reductions in HAE attack rates after ORLADEYO initiation, regardless of baseline attack frequency. Patients who experienced ≥5 baseline attacks/month had mean monthly attack rates decrease by 5.24 at 12 months (n=75) and 4.88 at 18 months (n=53) (both p<0.05). Patients with 0 attacks/month at baseline (n=39) maintained a low attack rate of 0 attacks/month during follow-up; 71 percent had 0 attacks/month at 12 months (n=14) and 70 percent had 0 attacks/month at 18 months (n=10)."

Real-world evidence • Hereditary Angioedema

Real-World Attack Rates Before and After Berotralstat Initiation Among Patients with Hereditary Angioedema with C1-Inhibitor Deficiency (Type I/II) Stratified by Monthly Baseline HAE Attack Frequency (GlobeNewswire) - "Patients with C1-INH deficiency (n=466) experienced statistically significant, sustained reductions in HAE attack rates after ORLADEYO initiation, regardless of baseline attack frequency. Patients who experienced ≥5 baseline attacks/month (n=82) had the largest reductions, with 6.20 fewer attacks/month at 12 months (n=45) and 6.37 fewer attacks/month at 18 months (n=36) (both p<0.05). Patients with 0 attacks/month at baseline (n=128) maintained a low attack rate of 0 attacks/month during follow up; 70 percent had 0 attacks/month at 12 months (n=60) and 85 percent had 0 attacks/month at 18 months (n=40)."

Real-world evidence • Hereditary Angioedema