Andembry (garadacimab) / CSL Behring - LARVOL DELTA

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

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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous and Intravenous Garadacimab Following Single-Dose Administration in Healthy Japanese and White Adults. (PubMed, J Clin Pharmacol) - "No anti-drug antibodies against garadacimab were reported. Consistent with pivotal phase 3 (VANGUARD) outcomes, no safety concerns and no difference in the safety profile of garadacimab were observed between healthy Japanese and White participants."

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

Clinical Meaningfulness of Improvements in Quality of Life Observed With Garadacimab Treatment in Patients Living With Hereditary Angioedema: Results From the Pivotal Phase 3 (VANGUARD) Study (ISPOR-EU 2024) - "Using FDA recommended methods for AE-QoL interpretation, patients with HAE are more likely to experience a clinically meaningful improvement in QoL when receiving garadacimab compared with placebo, exceeding both clinically meaningful thresholds."

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

A mechanistic model of in vitro plasma activation to evaluate therapeutic kallikrein-kinin system inhibitors. (PubMed, PLoS Comput Biol) - "The present model represents a valuable framework for studying the intricate interactions within the plasma KKS and provides a better understanding of the mechanism of action of various KKS-targeted therapies."

Journal • Preclinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Hypertension • Inflammation

CLINICAL EVIDENCE WITH GARADACIMAB DEMONSTRATES NO IMPACT ON HEMOSTASIS (ACAAI 2024) - "No abnormal bleeding events were observed with co-administration of hemostasis-impacting treatments in the Phase 3 pivotal (n=3/39, ticagrelor, aspirin, apixaban [n=1 each]) or OLE studies (n=8/159, aspirin [n=5], enoxaparin [n=2], rivaroxaban [n=1]). Clinical evidence demonstrated no garadacimab impact on hemostasis across HAE/COVID-19 studies, even when co-administered with hemostasis-impacting treatments in patients at increased bleeding risk (e.g. COVID-19). Observations align with absence of bleeding phenotype in patients with congenital deficiency of factor XII."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hereditary Angioedema • Infectious Disease • Novel Coronavirus Disease

BEING ATTACK-FREE WITH GARADACIMAB IMPROVES QUALITY OF LIFE IN PATIENTS WITH HEREDITARY ANGIOEDEMA (ACAAI 2024) - "In the Phase 3 OLE, garadacimab was associated with HRQoL improvements in garadacimab-naïve patients, and sustained HRQoL improvements in the previous garadacimab exposure cohort. The lowest impairment scores in AE-QoL were observed for attackfree patients in both cohorts. Mean AE-QoL total score at Day 1 and Month 12 for garadacimabnaïve patients and those with previous garadacimab exposure by attack-free status at Month 12, Phase 3 OLE"

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

GARADACIMAB ELICITS ATTACK-FREE STATUS IN HEREDITARY ANGIOEDEMA INDEPENDENT OF BASELINE CHARACTERISTICS (ACAAI 2024) - "In the pivotal Phase 3 (VANGUARD) study, patients with HAE achieved attack-free status with garadacimab independently of evaluated baseline patient characteristics. Regardless of baseline characteristics, patients with HAE have the potential to achieve attack-free status with garadacimab. Youden-index values, sensitivity, and specificity of baseline patient characteristics in the prediction of attack-free status"

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

PHARMACOMETRIC ANALYSIS SUPPORTS EARLY ONSET OF PROTECTION WITH GARADACIMAB AGAINST HEREDITARY ANGIOEDEMA ATTACKS (ACAAI 2024) - "PK data and ER predictions demonstrated garadacimab achieving steady-state exposures after LD (first administration) and maintaining steady−state exposures over subsequent once-monthly dosing intervals. LD maximizes the likelihood of reaching target therapeutic threshold resulting in early onset of protection against attacks as early as Week 1 after first administration."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

LOW INCIDENCE OF GARADACIMAB IMMUNOGENICITY WITH NO IMPACT ON EFFICACY, SAFETY OR PHARMACOKINETICS: INTEGRATED ANALYSIS (ACAAI 2024) - "Throughout the clinical development program, incidence and titers of garadacimab immunogenicity were low, with no observed impact on efficacy, safety, pharmacodynamics or pharmacokinetics. Monthly HAE attack rate and safety profile in patients with treatment-emergent ADAs*"

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

CHARACTERIZATION OF INJECTION SITERELATED ADVERSE EVENTS WITH GARADACIMAB IN PATIENTS WITH HEREDITARY ANGIOEDEMA (ACAAI 2024) - "In garadacimab Phase 3 studies, incidence of ISRs such as erythema, bruising and pruritus was low. The favorable injection-site tolerability with garadacimab may help reduce treatment burden during HAE LTP treatment."

Adverse events • Clinical • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Pain • Pruritus