Advances in therapy · 2026
Long-Term Integrated Safety and Efficacy of Garadacimab for Hereditary Angioedema Prophylaxis.
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Craig Timothy J, Guilarte Mar, Li Huamin Henry, Anderson John, Martinez Saguer Inmaculada, Jacobs Joshua S, Tachdjian Raffi, Farkas Henriette, Yang William H, Ohsawa Isao, Hakl Roman, Pollen Maressa, Pragst Ingo, Lawo John-Philip, Shetty Harsha, Nenci Chiara, Magerl Markus
Аннотация
INTRODUCTION: Garadacimab (monoclonal antibody inhibiting activated factor XII [FXIIa]) is approved for long-term prophylaxis (LTP) against hereditary angioedema (HAE) attacks. Due to the novelty of FXIIa inhibition and the lifelong need for HAE LTP, long-term evaluation of garadacimab is important. Pooling data from multiple studies can provide valuable insights into treatment effects over longer durations. We report the integrated summary of safety (ISS) and efficacy (ISE) of garadacimab LTP across the HAE clinical development program.
METHODS: The ISS comprised data from phase 2 (13-week placebo-controlled period, 75/200/600 mg monthly or 400 mg every 2 weeks; ≥ 44-week open-label period, 200/600 mg monthly; NCT03712228), pivotal phase 3 (6 months; 200 mg monthly; NCT04656418), and ≥ 12-month phase 3 open-label extension (OLE) studies (200 mg monthly; NCT04739059). The ISE comprised data from phase 3 studies. Endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) per protocol, and efficacy.
RESULTS: At data cutoff (June 15, 2024), median garadacimab exposure (ISS: any dose, n = 172) was 2.5 (range 0.2-5.5) years. Overall rates of TEAEs and garadacimab-related TEAEs were 2.8/patient-year and 0.2/patient-year, respectively. No deaths occurred; four TEAEs led to treatment discontinuation. Eleven patients experienced SAEs (0 garadacimab-related). No garadacimab-related AESIs were reported; one unrelated AESI was observed with garadacimab 600 mg (epistaxis; mild; resolved). The most common garadacimab-related TEAEs were mild/moderate injection-site reactions. In the ISE (median exposure 2.5 [range 0.3-3.2] years), the mean (95% confidence interval) monthly attack rate was 0.2 (0.1, 0.2) with garadacimab (n = 164), corresponding to a 94.9% (93.1, 96.7) reduction from run-in (3.5 [3.2, 3.9]).
CONCLUSION: These integrated data, representing the longest garadacimab exposure reported to date, confirm the favorable long-term safety profile of garadacimab (exposure ≤ 5.5 years), and durable efficacy with sustained protection against HAE attacks (exposure ≤ 3.2 years).
TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03712228, NCT04656418, NCT04739059.
METHODS: The ISS comprised data from phase 2 (13-week placebo-controlled period, 75/200/600 mg monthly or 400 mg every 2 weeks; ≥ 44-week open-label period, 200/600 mg monthly; NCT03712228), pivotal phase 3 (6 months; 200 mg monthly; NCT04656418), and ≥ 12-month phase 3 open-label extension (OLE) studies (200 mg monthly; NCT04739059). The ISE comprised data from phase 3 studies. Endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) per protocol, and efficacy.
RESULTS: At data cutoff (June 15, 2024), median garadacimab exposure (ISS: any dose, n = 172) was 2.5 (range 0.2-5.5) years. Overall rates of TEAEs and garadacimab-related TEAEs were 2.8/patient-year and 0.2/patient-year, respectively. No deaths occurred; four TEAEs led to treatment discontinuation. Eleven patients experienced SAEs (0 garadacimab-related). No garadacimab-related AESIs were reported; one unrelated AESI was observed with garadacimab 600 mg (epistaxis; mild; resolved). The most common garadacimab-related TEAEs were mild/moderate injection-site reactions. In the ISE (median exposure 2.5 [range 0.3-3.2] years), the mean (95% confidence interval) monthly attack rate was 0.2 (0.1, 0.2) with garadacimab (n = 164), corresponding to a 94.9% (93.1, 96.7) reduction from run-in (3.5 [3.2, 3.9]).
CONCLUSION: These integrated data, representing the longest garadacimab exposure reported to date, confirm the favorable long-term safety profile of garadacimab (exposure ≤ 5.5 years), and durable efficacy with sustained protection against HAE attacks (exposure ≤ 3.2 years).
TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03712228, NCT04656418, NCT04739059.