Long‐term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open‐label extension study
Bibliographic record
Abstract
BACKGROUND: Hereditary angioedema (HAE) is a chronic, unpredictable disease. Long-term prophylactic treatments that offer durable efficacy, safety, and convenience are required to assist patients in achieving complete disease control, per international guidelines. We report an interim analysis of an ongoing phase 3 (VANGUARD) open-label extension (OLE) study evaluating the long-term safety and efficacy of garadacimab for HAE prophylaxis. METHODS: Adults and adolescents aged ≥12 years with HAE previously participating in phase 2 and pivotal phase 3 (VANGUARD) studies were rolled over to an OLE, alongside newly enrolled patients. Patients received garadacimab 200 mg subcutaneously, once monthly for ≥12 months. The primary endpoint was treatment-emergent adverse events (TEAEs) in patients with C1 inhibitor deficiency/dysfunction. RESULTS: At data cut-off (February 13, 2023; N = 161), median (interquartile range) exposure was 13.8 months (11.9-16.3). For the primary endpoint, 133/159 patients experienced ≥1 TEAE (524 events), equivalent to 0.23 events/administration and 2.84 events/patient-year. Garadacimab-related TEAEs (13% of patients, 52 events) were most commonly injection-site reactions (ISRs). No deaths occurred. One patient discontinued treatment due to garadacimab-related moderate ISR. Most TEAEs were mild/moderate; three events were serious (COVID-19, two events; abdominal HAE attack, one event) and not garadacimab related. No abnormal bleeding, thromboembolic, severe hypersensitivity, or anaphylactic events were observed. Mean HAE attack rate decreased by 95% from the run-in period; 60% of patients were attack-free. Almost all patients (93%) rated their response to garadacimab as "good" or "excellent." CONCLUSION: Garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".