Berinert (C1 esterase inhibitor (human) IV) / CSL Behring - LARVOL DELTA

Systematic Literature Review of Recombinant C1 Esterase Inhibitor (rhC1-INH) and Other Products for the On-Demand Treatment of Hereditary Angioedema Attacks (ISPOR 2025) - "Eligible publications included phases 2, 3, and 4 randomized controlled trials (RCTs) and open-label extension (OLE) studies assessing HAE attacks in patients aged ≥12 years with the following interventions: Ruconest ® (conestat alfa), Firazyr ® (icatibant), Kalbitor ® (ecallantide), sebetralstat (KVD900), and Berinert (C1 esterase inhibitor, human). The study populations and end point definitions used in clinical trials assessing acute HAE treatments have changed over time. Key study differences included route of administration, trial setting, time of treatment, attack severity at enrollment, attack location, redosing and rescue therapy criteria, patient-reported outcome assessments, and outcome definitions. Further investigation is warranted to evaluate these differences and determine whether they affected study outcomes."

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

Safe Off-Label Use of Icatibant as Treatment for Acute Hereditary Angioedema Attacks in a Pediatric Patient (CIS 2025) - "Case Description: Despite previous success with Berinert for abortion of peripheral attacks, this patient's family was frustrated with long wait times and care in the ED...Eventually, the patient was approved through her insurance to use icatibant 15 mg SQ for attacks, and lanadelumab was also initiated for maintenance therapy given increasing attack frequency through manufacturer assistance and eventual insurance approval through assistance of a multidisciplinary team... This case illustrates the potential for safe off-label use of icatibant down to 2 years of age for acute attacks of HAE. Penn State Health has been prescribing and administering icatibant down to 2 years of age despite being off-label, and we hope this work encourages FDA approval and other institutions to make icatibant available as a weight-adjusted dose as an option for abortive treatment until oral rescue medications are available to reduce drug burden in pediatrics."

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

Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (IMPROVE TRIAL) (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

New P2 trial • Transplantation

Berinert (C1INH) vs Placebo for DGF/IRI (clinicaltrials.gov) - P1/2 | N=45 | Completed | Sponsor: Cedars-Sinai Medical Center | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Oct 2024

Trial completion • Trial completion date • Cardiovascular • Chronic Kidney Disease • Nephrology • Reperfusion Injury

HEREDITARY ANGIOEDEMA TYPE II WITH NORMAL C4 LEVELS (ACAAI 2024) - "She was initially placed on lanadelumab and icatibant but only saw partial response. She was transitioned to C1 inhibitor replacement therapy with Haegarda and Berinert and saw significant improvement in symptoms...This case demonstrates how complete evaluation should be done when clinical suspicion remains high. Periorbital Edema in Patient with HAE Type II"

Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Immunology • Inflammatory Arthritis • Pain • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Urticaria

Hereditary angioedema: when the surgical site is the airway (Euroanaesthesia 2024) - "The patient experienced recurrent AE episodes and was medicated with tranexamic acid (500 mg/day) and icatibant (15 mg as needed). One hour before extraction, 20 U/Kg of Berinert was administered. General anesthesia (GA) with sevoflurane, rocuronium (0.6 mg/Kg), and a cuffed RAE endotracheal tube proceeded uneventfully...Teamwork is essential for successful HA management, necessitating collaboration between immunologists and the anesthesia and surgical teams. Learning Points : The approach to HA in surgical settings involves measures to prevent AE and the necessity for extended postoperative monitoring."

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

mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions. (PubMed, Int J Mol Sci) - "Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway...Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or..."

Journal • Cardiovascular • Infectious Disease • Inflammation • Novel Coronavirus Disease • CXCL8 • IFNG • IL1B • IL6 • TNFA

Type III Hereditary Angioedema due to rare F12 gene mutation (AAAAI 2024) - "The testing revealed he had the same mutation as his mother and aunt, and we recommended as needed abortive treatment with C1-INH (Berinert). The patient has not developed any angioedema symptoms or need for the medication so far."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Tenecteplase-associated orolingual angioedema: A case report and literature review. (PubMed, Am J Health Syst Pharm) - "Although rare, OA is a potentially life-threatening complication of tenecteplase therapy and requires prompt pharmacological intervention to optimize patient outcomes. Currently, no single agent or treatment algorithm exists that has shown significant efficacy or safety in the setting of thrombolytic-associated OA. Until data are available for C1 esterase inhibitors in this application, these inhibitors should only be considered if there is continued symptom progression after intravenous administration of corticosteroids and antihistamines."

Journal • Review • Cardiovascular • Hypertension • Ischemic stroke • Pulmonary Disease

Vision loss due to atypical bilateral edema of the optic nerve in a patient with hereditary angioedema: A case report. (PubMed, Eur J Ophthalmol) - "Patients affected by HAE may show atypical presentation with edema of the optic nerves without involvement of the optic nerve head. They may significantly benefit from prophylactic and chronic treatment with C1-esterase inhibitor."

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

Berinert (C1INH) vs Placebo for DGF/IRI (clinicaltrials.gov) - P1/2 | N=40 | Active, not recruiting | Sponsor: Cedars-Sinai Medical Center | Trial completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Cardiovascular • Chronic Kidney Disease • Nephrology • Reperfusion Injury

"and Berinert, Ruconest, Haegarda and now oral Orladeyo do the same." (@670rv)

Berinert (C1INH) vs Placebo for DGF/IRI (clinicaltrials.gov) - P1/2 | N=40 | Active, not recruiting | Sponsor: Cedars-Sinai Medical Center | Trial completion date: Jul 2023 ➔ Dec 2023

Trial completion date • Cardiovascular • Chronic Kidney Disease • Nephrology • Reperfusion Injury

Berinert (C1INH) vs Placebo for DGF/IRI (clinicaltrials.gov) - P1/2 | N=40 | Active, not recruiting | Sponsor: Cedars-Sinai Medical Center | Trial completion date: Dec 2022 ➔ Jul 2023

Trial completion date • Cardiovascular • Chronic Kidney Disease • Nephrology • Reperfusion Injury

Concurrent HAE abdominal episode and acute appendicitis in a 7 year old male (AAAAI 2023) - "Given a high suspicion for acute abdomen in the setting of HAE swelling, 20 units/kg Berinert were administered along with antibiotics parenterally...Laparoscopic appendectomy was uncomplicated and suggestive of acute appendicitis intra-operatively and later confirmed on pathology examination. C1 esterase inhibitor level and function ultimately returned as undetectable (<8 mg/dL) and 16%, respectively."

Gastroenterology • Gastrointestinal Disorder • Pain

SPECIFIC MEASUREMENT OF ACTIVATED COAGULATION FACTORS BY COMPLEX FORMATION WITH PROTEASE INHIBITORS (EAHAD 2023) - "Here we describe the use of solid phase-bound inhibitors (tissue factor pathway inhibitor [TFPI], corn trypsin inhibitor [CTI], and C1-inhibitor [C1-inh]) to measure the activated coagulation factors factor X (FXa), factor XII (FXIIa) and factor XI (FXIa) by formation of the immobilized inhibitor-protease complex and its immunological detection by protease-specific antibody. TFPI (R&D Systems), CTI (ERL) and purified plasma-derived C1-inh (Berinert, CSL Behring), diluted in phosphate-buffered saline (PBS) to a concentration of 10 μg/mL were coated to Maxisorp F96 plates at 4°C overnight. The high selectivity obtained in these assays depends on the protease specificity of the immobilized inhibitor, which is further complemented by the specificity of the anti-zymogen detection antibody used to measure the amount of the inhibitor-protease complex bound to the solid phase."

Immunology

Geriatric Pharmacotherapy Case Series: Recurrent Angioedema Following Discontinuation of ACE Inhibitor Therapy. (PubMed, Sr Care Pharm) - "This case describes an older man with a history of chronic obstructive pulmonary disease, hypothyroidism, diabetes mellitus, hypertension, and heart failure who presented from an assisted living facility with recurrent angioedema 12 days after an initial episode of angioedema where his ACEI therapy (enalapril) was discontinued. Assessment Empiric methylprednisolone, diphenhydramine, intramuscular epinephrine, intravenous C1 esterase inhibitor Berinert®, and two units of fresh frozen plasma was given in the emergency department...Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important for both providers and pharmacists to provide appropriate diagnosis and monitoring. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence following drug discontinuation."

Journal • Cardiovascular • Chronic Obstructive Pulmonary Disease • Complement-mediated Rare Disorders • Congestive Heart Failure • Critical care • Diabetes • Endocrine Disorders • Heart Failure • Hereditary Angioedema • Hypertension • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases

ANGIOEDEMA PREVENTING EXTUBATION IN A CASE OF ACQUIRED C-1 ESTERASE DEFICIENCY (SCCM 2023) - "Epinephrine and Solumedrol were administered, however the neck swelling worsened and the patient was intubated for airway protection...Glucocorticoids were ineffective as the patient had a reported allergy to Prednisone, therefore were further avoided...If Berinert is ineffective, some immunologists and allergists have seen favorable outcomes and recommend treatment with the kallikrein inhibitor, ecallantide and the bradykinin B2 antagonist icatibant. To date, therapies targeted at prevention of angioedema in acquired cases have not been as successful as in hereditary forms, therefore, treatment is directed at the underlying condition, such as immunotherapy or chemotherapy for CLL."

Clinical • Allergy • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology

Effects of C1-INH Treatment on Neurobehavioral Sequelae and Epileptogenesis Following Traumatic Brain Injury (AES 2022) - "One hour after brain injury, mice were randomly allocated to receive a single intravenous injection of human plasma-derived C1-INH (15.0 IU Berinert®; CSL Behring) or vehicle solution... This study confirmed the neuroprotective and anti-inflammatory effects of C1-INH. C1-INH treatment improved neurobehavioral outcomes, and exhibited a disease-modifying effect on epileptogenesis after TBI. The safety profile of C1-INH from extensive clinical experience supports the possibility of repurposing C1-INH to combat severe TBI."

CNS Disorders • Epilepsy • Inflammation • Psychiatry • Vascular Neurology • TNFA

C1-Inhibitor (INH) for Refractory Antibody Mediated Renal Allograft Rejection (clinicaltrials.gov) - P2; N=1; Completed; Sponsor: NYU Langone Health; Enrolling by invitation ➔ Completed; Trial completion date: Oct 2021 ➔ Oct 2018; Trial primary completion date: Oct 2021 ➔ Oct 2018

Trial completion • Trial completion date • Trial primary completion date • Antibody-mediated Rejection • CCNB1

Robotic Gynecological Surgery In A Patient With Hereditary Angioedema. (ASA 2022) - "After expert consultation, prophylactic Icabitant (Firazyr) and C1 esterase inhibitor (Haegarda) were continued. Availability of rescue C1 esterase inhibitor (Berinert) was confirmed...Good multimodal pain management and PONV prophylaxis may aid in recognition of postoperative angioedema. Postoperatively, she was admitted for observation, had no acute attacks, and was discharged the following day."

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

Idiopathic Angioedema After Reverse Total Shoulder Arthroplasty: A Case Report (ASA 2022) - "Progression of symptoms were successfully prevented after treatment with epinephrine, hydrocortisone, Berinert (C1 esterase inhibitor), diphenhydramine, albuterol, humidified oxygen, and esmolol. The patient was carefully monitored in the recovery period for recurrent episodes of angioedema, and was discharged after three days of continued improvement."

Clinical • Anesthesia • Cardiovascular • Orthopedics

Perioperative management of a patient with type II hereditary angioedema: be prepared and be vigilant (Euroanaesthesia 2022) - "On the day of the procedure, the urgent administration of a bradykinin B2 receptor antagonist (Icatibant®) in case of acute crisis was planned and the patient received prophylactic therapy with 1000IU of plasma-derived C1 esterase inhibitor (Berinert®). Spinal anesthesia with 12,5mg levobupivacaine and 2,5mcg sufentanil was performed. The procedure lasted close to an hour and postoperative analgesia was accomplished with 1g acetaminophen...Acute exacerbations may not respond well to antihistamines, glucocorticoids and epinephrine and urgent therapy with recombinant C1-inhibitor drugs or bradykinin receptor antagonists may be necessary. Alternatives include high doses of androgens, tranexamic acid, adequate fluid therapy and intensive support. The supervising clinician must be prepared to recognize and manage angioedema and intubation should be attempted immediately if stridor and/or signs of respiratory arrest are present."

Clinical • Anesthesia • Atrial Fibrillation • Cardiovascular • Complement-mediated Rare Disorders • Gynecology • Hereditary Angioedema

Hereditary angioedema- 6 case series (EADV-Sp 2022) - "HAE typically do not respond to administration of antihistamines, glucocorticoids, or epinephrine or adrenaline. For acute attacks of the extremities, respiratory airway and gastrointestinal tract, plasma-derived C1-INH (Berinert) and icatibantum are effective...Discussion Hereditary angioedema is a very rare genetic disease transmitted in an autosomal dominant pattern that requires mandatory familial screening even before the onset of the clinical manifestations. Earlier diagnosis and treatment of hereditary angioedema can prevent HAE-associated mortality."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Gastrointestinal Disorder • Genetic Disorders • Hereditary Angioedema • Rare Diseases

Efficacy and Safety of GNR-038 vs Berinert® in Patients With Hereditary Angioedema (clinicaltrials.gov) - P2/3 | N=0 | Withdrawn | Sponsor: AO GENERIUM | N=50 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema