Andembry (garadacimab) / CSL Behring - LARVOL DELTA

A novel role for SIX1 and EYA2 and a novel EYA2 inhibitor in myeloid leukemogenesis (ASH 2025) - "SIX1, together with itscofactor Eyes Absent 2 (EYA2), a protein tyrosine phosphatase, is involved in cell proliferation andembryogenesis and transcriptionally activates developmental genes... We first determined that increased SIX1 expression is associated with worse event free survival (EFS) andoverall survival, while EYA2 correlates solely with EFS using the Therapeutically Applicable Research toGenerate Effective Treatments (TARGET) database, which exploits a multiomic approach to evaluateprofiles of multiple cancers. We next queried the Broad Institute Cancer Dependency Map and identifiedincreased SIX1 expression in SHI-1 and OCI-M2 AML cell lines; neither displayed increased EYA2expression. SIX1 expression in these cells was validated by immunoblot, and shRNA knockdown of SIX1reduced proliferation in both cell lines."

Acute Myelogenous Leukemia • Esophageal Cancer • Hematological Malignancies • Leukemia • Ovarian Cancer • KMT2A • MLLT10 • SIX1

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

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

Matching-Adjusted Indirect Comparison Between Garadacimab and Donidalorsen for Long-Term Prophylaxis in Hereditary Angioedema (ISPOR-EU 2025) - P3 | "These findings demonstrate that garadacimab may provide improved therapeutic benefit compared to donidalorsen for LTP in HAE."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Long-Term Integrated Safety and Efficacy of Garadacimab for Hereditary Angioedema Prophylaxis up to 5.5 years (ACAAI 2025) - "In the ISE (median exposure 2.5 years; range 0.3–3.2), the mean (95% confidence interval) monthly attack rate was 0.15 (0.1–0.2) with garadacimab long-term prophylaxis (n=164), corresponding to a 94.9% (93.1–96.7) reduction in attack rate from run-in (3.54 [3.2–3.9]). Conclusion These data confirm the favorable long-term safety profile of garadacimab up to 5.5 years of exposure, as well as durable efficacy with sustained protection against HAE attacks up to 3.2 years of exposure."

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

Garadacimab Normalizes Activated Factor XII-Mediated Kallikrein Activity and D-Dimer Levels (ACAAI 2025) - "Conclusion FXIIa-mediated kallikrein activity and D-dimer levels tended to normalize in patients with HAE receiving garadacimab. These data provide a mechanistic basis for the observed clinical efficacy of garadacimab as LTP against HAE attacks."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Product Theater 4 (non-CME) - CSL Behring : ANDEMBRY® (garadacimab-gxii): A Breakthrough New Treatment in Long-Term Prophylaxis (ACAAI 2025) - "Sponsored by CSL Behring Description This interactive presentation will explore a patient's journey to highlight the e??icacy and safety of ANDEMBRY—a newly approved, long-term prophylactic treatment. Also visit CSL Behring at Booth #518 ."

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

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

Post Study Access of CSL312 (Garadacimab) for Pediatric Participants With Hereditary Angioedema Who Have Completed the CSL312_3003 Study (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: CSL Behring

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

A Phase 1 Randomized Study: Garadacimab Pharmacokinetics, Safety, and Tolerability After Administration via Autoinjector/Pre-Filled Pen Versus Pre-Filled Syringe in Healthy Participants. (PubMed, J Clin Pharmacol) - "Garadacimab 200 mg administered as a single subcutaneous dose via AI/PFP had a consistent safety and tolerability profile to that administered via PFS. These findings support administration of garadacimab via AI/PFP, providing at-home convenience for patients and physicians."

Journal • P1 data • PK/PD data • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Garadacimab in hereditary angioedema due to normal C1INH with F12/PLG mutations. (PubMed, J Allergy Clin Immunol) - "Garadacimab showed a favorable safety profile in all 6 patients with HAE-nC1INH. Garadacimab also demonstrated efficacy in 2 of the 2 patients with HAE-FXII; a reduction in AR was observed in 1 of the 2 patients with HAE-PLG."

Journal • Cardiovascular • Complement-mediated Rare Disorders • 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 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting

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

Matching-adjusted indirect comparison between garadacimab and lanadelumab for the long-term prophylactic treatment of patients with hereditary angioedema. (PubMed, J Comp Eff Res) - P2, P3 | " These MAICs showed improved efficacy and QoL with garadacimab compared with lanadelumab across multiple endpoints. These findings demonstrate that garadacimab may provide improved therapeutic benefit compared with lanadelumab in the long-term prophylactic treatment of patients with HAE."

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

ANDEMBRY (garadacimab-gxii). (PubMed, Clin Ther) - No abstract available

Journal

Pharmacological characteristics and clinical trial results of garadacimab (anti-activated factor XII monoclonal antibody) for long-term prophylaxis of hereditary angioedema (PubMed, Nihon Yakurigaku Zasshi) - "The proportion of patients who remained attack-free during the 6-month was 62% in garadacimab and 0% in placebo, and effect after the first dose was maintained throughout the study period. Since this drug is administered subcutaneously once a month with autoinjector, reduction of patients' burden is also expected."

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

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