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

Non-CME Corporate Forum - BioCryst Pharmaceuticals, Inc. : ORLADEYO® (berotralstat): Individualized Management Across the Patient and Family Journey (ACAAI 2026) - "Also visit BioCryst Pharmaceuticals, Inc. at Booth #1500."

Clinical

CareMed, an independent specialty pharmacy, has been selected as a pharmacy partner by BioCryst Pharmaceuticals for Orladeyo (berotralstat), a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 2 years and older (GlobeNewswire)

Commercial • Hereditary Angioedema

Evaluating deucrictibant for the treatment of hereditary angioedema. (PubMed, Expert Opin Pharmacother) - "Over the past 6 years two oral therapies have been developed for HAE to include berotralstat for long term prophylaxis (LTP) and sebetralstat for on-demand therapy (ODT). Deucrictibant is a promising therapeutic agent with a well-defined mechanism of action. Published and ongoing clinical studies demonstrate favorable safety, tolerability, and efficacy profiles for both LTP and ODT, offering a convenient oral alternative that may reduce treatment burden and improve patient quality of life."

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

BioCryst Pharmaceuticals, Inc…announced that Japan’s Ministry of Health, Labor and Welfare (MHLW) has granted marketing approval for once-daily ORLADEYO (berotralstat) for prophylactic therapy in pediatric patients with hereditary angioedema (HAE) aged 2 to <12 years. (GlobeNewswire) - "This approval is based on positive interim results from the APeX-P clinical trial, the largest trial of long-term prophylaxis (LTP) in pediatric patients with HAE, evaluating the pharmacokinetics, safety and efficacy of ORLADEYO in patients aged 2 to <12 years with HAE due to C1-inhibitor deficiency."

Japan approval • Hereditary Angioedema

Berotralstat Tolerability and Effectiveness in Hereditary Angioedema: Berolife Study Results. (PubMed, Clin Transl Allergy) - "Berotralstat was generally well tolerated with a tolerability profile consistent with prior clinical trials. Significant reductions in monthly HAE attack rates were observed, confirming its effectiveness in real-world settings."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Gastroenterology • Gastrointestinal Disorder • Hereditary Angioedema • Pain

The evolving treatment landscape for hereditary angioedema in Sweden. (PubMed, Front Immunol) - "Among patients with ≥12 months on modern LTP (n=69) who had at least one ODT dispensation event during their most recent 12 months of treatment (n=46/59 for lanadelumab; n=8/9 for berotralstat), the mean number of ODT packages dispensed-in addition to emergency stock ODT-was 4.3 per patient on lanadelumab and 6.5 per patient on berotralstat. This study provides valuable insights into real-world dispensation patterns of HAE drugs in Sweden. Despite the availability of modern LTP therapies, there remains relatively high ODT dispensation events, suggesting ongoing unmet need and underscoring the importance of optimizing prophylactic strategies to achieve total disease control."

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

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

Berotralstat During Pregnancy in a Patient With Hereditary Angioedema. (PubMed, J Investig Allergol Clin Immunol) - No abstract available

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

Sebetralstat for breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis in KONFIDENT-S. (PubMed, J Allergy Clin Immunol Glob) - P3 | "This interim analysis of the KONFIDENT-S study evaluated long-term safety and effectiveness of oral sebetralstat 600 mg for attacks of hereditary angioedema with C1-inhibitor deficiency in participants receiving LTP with lanadelumab, berotralstat, or C1 inhibitor. Sebetralstat was well tolerated and enabled early on-demand treatment of attacks in patients with hereditary angioedema with C1-inhibitor deficiency receiving LTP. Treatment of breakthrough attacks with sebetralstat resulted in rapid symptom relief, reduction in attack severity, and complete attack resolution, regardless of LTP mechanism of action."

Journal • 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

Clinical experience with berotralstat in patients with hereditary angioedema: an Italian case series from the ITACA cohort. (PubMed, Eur Ann Allergy Clin Immunol) - "The latest international guidelines recommend as first-line options for LTP plasma-derived C1-INH, lanadelumab, and berotralstat. Conclusions. Patient engagement, awareness of androgen risks, transition strategies and drug-interaction evaluation are essential to guide individualized LTP choices."

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

The Neglected Older Adults in Hereditary Angioedema: Insights From the ITACA Registry. (PubMed, Clin Transl Allergy) - "Older patients with HAE-C1INH constitute a relevant subgroup, characterized by persistent disease activity and comorbidities. The availability of new therapies and guideline recommendations are driving an increase in LTP use, although shifting from older non-specific treatments, especially androgens, is still incomplete."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Coronary Artery Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Hepatitis B • Hepatitis C • Hereditary Angioedema • Hypertension • Metabolic Disorders • Oncology • Rare Diseases

Real-world treatment patterns and clinical burden of patients with hereditary angioedema treated with long-term prophylaxis. (PubMed, Orphanet J Rare Dis) - "Although recently available LTP can partly reduce the clinical burden of patients with HAE, novel therapies are needed to further alleviate this burden."

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

Probiotic supplementation to mitigate berotralstat gastrointestinal side effects: a multicenter case series from the ITACA network. (PubMed, Front Immunol) - "Probiotic co-administration during early berotralstat therapy was accompanied by a low incidence of GI side effects, while clinical effectiveness was maintained. These preliminary findings support further controlled studies to validate probiotics as a supportive strategy for improving the tolerability of berotralstat."

Adverse events • Journal • 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

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

Berotralstat and Health-Related Quality of Life in Hereditary Angioedema: Pooled Analysis of the APeX-2 and APeX-J Trials. (PubMed, Clin Exp Allergy) - "Berotralstat significantly improved HRQoL versus placebo through 24 weeks and showed long-term beneficial effects through 96 weeks."

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

Consensus of Mexican experts on long-term prophylaxis in patients with hereditary angioedema in Mexico (PubMed, Rev Alerg Mex) - "HAE prophylaxis management in Mexico appears aligned with contemporary standards, yet sustained and individualized implementation remains limited by structural access and supply constraints. Key priorities include strengthening timely diagnosis, ensuring continuous access to targeted therapies, and standardizing follow-up in routine clinical care."

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

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