Andembry (garadacimab) / CSL Behring - LARVOL DELTA

Effect of factor XIIa or XIa inhibitors on catheter-initiated thrombin generation: an in vitro study (ISTH 2025) - "Aims We investigated the effect of garadacimab, abelacimab, asundexian, milvexian, apixaban, dabigatran, fondaparinux and enoxaparin, compared to UFH, using a previously validated in vitro model of catheter-initiated thrombin generation (TG) in platelet-rich plasma (PRP). Adding garadacimab and abelacimab directly to collection tubes, rather than to PRP, resulted in greater efficacy, with LT increasing by 89% and 32%, respectively; in this setting, the IC50 were 25 µg/mL and 12.5 µg/mL, respectively. Table or Figure Upload"

Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

Effect of heparins, DOACs, and FXII/FXI inhibitors on catheter-initiated thrombin generation in PRP: an in vitro study. (PubMed, J Thromb Haemost) - "Heparins were by far the most effective anticoagulants in our in vitro model. Factor XIIa and XI(a) inhibitors did not adequately prevent coagulation on the studied artificial surface. DOACs and fondaparinux showed limited efficacy, aligning with clinical observations."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Thrombosis

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

U.S. Food and Drug Administration Approves CSL's ANDEMBRY (garadacimab-gxii), the Only Prophylactic Hereditary Angioedema (HAE) Treatment Targeting Factor XIIa with Once-Monthly Dosing for All Patients From the Start (PRNewswire) - "Global biotechnology leader CSL...announced the U.S. Food and Drug Administration (FDA) approved ANDEMBRY (garadacimab-gxii), the only treatment targeting factor XIIa for prophylactic use to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. By targeting factor XIIa, a plasma protein that plays a key role in attacks of swelling in people with HAE, ANDEMBRY inhibits the top of the HAE cascade to prevent HAE attacks. ANDEMBRY, the only treatment to offer once-monthly dosing from the start for all patients, is a subcutaneous self-injection delivered in 15 seconds or less via an autoinjector with a citrate-free formula....The approval is supported by data from the pivotal placebo-controlled Phase 3 VANGUARD trial evaluating the efficacy and safety of ANDEMBRY."

FDA approval • Hereditary Angioedema

GREAT: A Study Investigating the Effectiveness and Safety of Garadacimab for Treating Patients With Hereditary Angioedema (HAE) (clinicaltrials.gov) - P=N/A | N=200 | Not yet recruiting | Sponsor: CSL Behring

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

CSL312_3003 Safety and Pharmacokinetic Study in Subjects 2 to 11 Years of Age With Hereditary Angioedema (clinicaltrials.gov) - P3 | N=20 | Active, not recruiting | Sponsor: CSL Behring | Trial completion date: Nov 2026 ➔ Dec 2025 | Trial primary completion date: Nov 2026 ➔ Dec 2025

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

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

The potential of factor XII inhibitors in preventing hereditary angioedema attacks. (PubMed, Expert Opin Biol Ther) - "By synthesizing findings from both preclinical and clinical studies and real-world observational studies, the review highlights the efficacy, safety, and practical benefits of FXII inhibitors, such as garadacimab...Despite its potential, uncertainties remain regarding long-term safety, cost, and accessibility. Future research will help redefine the role of FXII inhibition in advancing personalized care and improving the quality of life for patients with HAE."

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

Becoming attack-free further improves health-related quality of life in patients with hereditary angioedema receiving garadacimab. (PubMed, Allergy Asthma Proc) - P3 | "After garadacimab exposure in previous studies, improvements were maintained in the phase III OLE study. Attack-free patients had the greatest HRQoL improvements, bringing them closer to complete disease control and life normalization.Clinical trials NCT04656418, NCT04739059, www.clinicaltrials.gov."

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

Garadacimab improves long-term health-related quality of life in patients with hereditary angioedema. (PubMed, Allergy Asthma Proc) - P3 | "Improvements in WPAI:GH scores were consistent with AE-QoL and TSQM II. Garadacimab elicited clinically meaningful long-term improvements in HRQoL, work productivity, and treatment satisfaction in patients with HAE, which brought them closer to complete disease control and normalization of life.Clinical trial NCT04739059, clinicaltrials.gov."

HEOR • Journal • Allergy • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Immunology

Safety Study in Subjects ≥ 12 Years of Age With Hereditary Angioedema Switching to Garadacimab (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting

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

Garadacimab: First Approval. (PubMed, Drugs) - "In the USA and Canada, regulatory review of garadacimab is currently underway. This article summarizes the milestones in the development of garadacimab leading to this first approval for prevention of recurrent hereditary angioedema attacks in adult and adolescent patients aged ≥ 12 years."

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

CSL Launches ANDEMBRY for the Prevention of Acute Attacks in Hereditary Angioedema (HAE) in Japan (CSL Behring Press Release) - "CSL Behring K.K....today announced that it launched ANDEMBRY Subcutaneous Injection 200 mg Pen (garadacimab), a novel human anti-activated Factor XII monoclonal antibody for the Prevention of Acute Attacks of Hereditary Angioedema (HAE) in Japan...On February 20, 2025, CSL received manufacturing and marketing approval for ANDEMBRY from Japan’s Ministry of Health, Labour and Welfare (MHLW), based on efficacy and safety data from the global Phase III 'VANGUARD' trial 1 and its open-label extension study2, which included HAE patients, including those from Japan."

Launch Japan • Hereditary Angioedema

Population Pharmacokinetic/Pharmacodynamic and Exposure-Response Modeling of Garadacimab in Healthy Volunteers and Patients With Hereditary Angioedema. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Use of a loading dose (two 200 mg SC injections) as the first administration achieved steady-state PK exposures and PD response, with 85% of patients having exposures surpassing the therapeutic threshold. The models support the use of garadacimab 200 mg SC once-monthly dosing in patients aged ≥ 12 years, with no need for dose adjustments, and indicate that, due to the achievement of garadacimab steady-state exposures after the first administration, the use of a loading dose may facilitate the early onset of protection against HAE attacks, as observed in clinical studies."

Journal • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

CSL Receives Approval in Japan for ANDEMBRY (garadacimab) Subcutaneous (S.C.) Injection 200mg Pens, a Novel Human Anti-Activated Factor XII Monoclonal Antibody for the Prevention of Acute Attacks of Hereditary Angioedema (HAE) (PRNewswire) - "CSL Behring K.K...today announced that it has received manufacturing and marketing approval from Japan's Ministry of Health, Labour and Welfare (MHLW) for ANDEMBRY (garadacimab) Subcutaneous (S.C.) Injection 200mg Pens. The product is approved for the prevention of acute attacks of hereditary angioedema (HAE) and is the first pre-filled pen presentation for once-monthly subcutaneous administration for long-term prophylaxis of HAE. The approval in Japan follows additional recent approvals received in Australia, the United Kingdom, and the European Union...The approval of ANDEMBRY is based on the efficacy and safety data from the pivotal international Phase 3 VANGUARD trial and its open-label extension study."

Japan approval • Hereditary Angioedema

Clinical Study Experience Suggests No Impact On Hemostasis Among Patients With Hereditary Angioedema Receiving Garadacimab And Undergoing Surgical/Medical Procedures (AAAAI-WAO 2025) - P3 | "Conclusions Clinical study evidence suggests that inhibiting FXIIa with garadacimab does not impact hemostasis in patients with HAE undergoing surgical/medical procedures. This is consistent with observations of an absent bleeding phenotype in individuals with a congenital factor XII deficiency."

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

Efficacy And Safety of Garadacimab Via Autoinjector/Pre-Filled Pen For Hereditary Angioedema Long-Term Prophylaxis – Interim Results From A Phase 3 Open-Label Extension Study (AAAAI-WAO 2025) - P3 | "No adverse events of special interest per protocol (thromboembolic/abnormal bleeding events, severe hypersensitivity/anaphylaxis) were observed. Conclusions Long-term prophylaxis with garadacimab administered via AI/PFP showed durable protection against HAE attacks with a favorable safety profile."

Clinical • P3 data • P3 data: top line • Cardiovascular • Complement-mediated Rare Disorders • Food Hypersensitivity • Hereditary Angioedema • Immunology • Musculoskeletal Diseases • Orthopedics

Garadacimab Real-World Treatment Outcomes Of Effectiveness, Safety, And Quality-Of-Life In Patients With HAE (GREAT) Study Design (AAAAI-WAO 2025) - "Estimated study completion is 2029. Conclusions The GREAT study will gather the first real-word data on effectiveness, safety, HRQoL, and HCRU in patients with HAE receiving garadacimab LTP in routine clinical practice."

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

European Commission Approves CSL’s ANDEMBRY (garadacimab) for the Prevention of Recurrent Attacks of Hereditary Angioedema (HAE) (PRNewswire) - "Global biotechnology leader CSL...today announced that the European Commission (EC) has approved ANDEMBRY (garadacimab), the first and only once-monthly treatment targeting factor XIIa to prevent attacks of hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older. ANDEMBRY inhibits plasma protein factor XIIa, which initiates the cascade of events leading to angioedema at various sites of the body. ANDEMBRY reinforces CSL's decades-long commitment to delivering innovative treatment modalities to the HAE community and comes with a convenient patient-centric pre-filled pen (auto-injector) enabling subcutaneous self-injection...The approval of ANDEMBRY is based on the efficacy and safety data from the pivotal international Phase 3 VANGUARD trial and its open-label extension study."

EMA approval • Hereditary Angioedema

Long-Term Efficacy Of Garadacimab For Hereditary Angioedema In Patients With Or Without Prior Exposure In A Phase 3 Open-Label Extension Study (AAAAI-WAO 2025) - P3 | "Most patients were attack-free (66.2% [n=47] with prior garadacimab exposure and 54.4% [n=49] garadacimab-naïve patients). Conclusions Long-term prophylaxis with garadacimab provided durable protection against HAE attacks throughout the OLE in patients with prior garadacimab exposure and garadacimab-naïve patients, consistent with previous findings."

Clinical • P3 data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

No Impact Of Concomitant Medication Use On Pharmacokinetic And Safety Profiles Of Garadacimab In Hereditary Angioedema (AAAAI-WAO 2025) - "Garadacimab's safety profile was consistent with that of patients who did not receive concomitant medication. Conclusions Use of concomitant medications had no impact on PK or safety profiles of garadacimab as long-term prophylaxis for HAE."

Clinical • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pain

Safety And Efficacy Of Garadacimab For Hereditary Angioedema Prophylaxis In Patients Aged ≥65 Years (AAAAI-WAO 2025) - "In the integrated efficacy set (n=14), mean (standard deviation) monthly attack rate was 0.06 (0.08) with garadacimab vs 2.56 (1.30) during run-in period (97.3% reduction); 7/14 patients (50%) were attack-free (maximum exposure: 1.7 years). Conclusions Consistent with the overall study populations, garadacimab demonstrated long-term efficacy and a favorable safety profile in patients aged ≥65 years."

Clinical • Asthma • Cardiovascular • Complement-mediated Rare Disorders • Dyslipidemia • Hereditary Angioedema • Hypertension • Immunology • Metabolic Disorders • Respiratory Diseases

Safety Study in Subjects ≥ 12 Years of Age With Hereditary Angioedema Switching to Garadacimab (clinicaltrials.gov) - P4 | N=30 | Not yet recruiting | Sponsor: CSL Behring

New P4 trial • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective. (PubMed, Front Immunol) - "The dynamics of the components are examined under three distinct conditions: the disease state representing symptomatic COVID-19 state, an intervened disease state marked by reduced levels of regulators, and drug interventions including heparin, tranexamic acid, avdoralimab, garadacimab, and tocilizumab. In conclusion, this study explains the regulatory mechanisms of the hemostatic and complement systems and illustrates how the biopathway machinery sustains the balance between activation and inhibition. The knowledge that we have acquired could contribute to designing therapies that target the hemostatic and complement systems."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis • A2M • IL6R

CSL Receives Positive CHMP Opinion for Garadacimab in Hereditary Angioedema (HAE) (PRNewswire) - "Global biotechnology leader CSL...announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a marketing authorization for garadacimab as a once-monthly prophylactic treatment for hereditary angioedema (HAE) in adult and adolescent patients aged 12 years and older. Garadacimab is a monoclonal antibody that targets activated factor XII (factor XIIa), a plasma protein that plays a key role in attacks of swelling in people with HAE, thereby inhibiting the HAE cascade at the top to prevent HAE attacks. The final European Commission (EC) decision is expected in Q1 2025."

CHMP • Hereditary Angioedema