Evidence map›Paper›PMID 42268494›Full record

ArticleAdvances in therapy2026

Long-Term Integrated Safety and Efficacy of Garadacimab for Hereditary Angioedema Prophylaxis.

Timothy J Craig, Mar Guilarte, Huamin Henry Li, John Anderson, Inmaculada Martinez Saguer, Joshua S Jacobs, Raffi Tachdjian, Henriette Farkas, William H Yang, Isao Ohsawa and 7 more

3 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advances in therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03712228 phase2completednot on this map

A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema

TypeinterventionalSponsorCSL BehringRan2018 to 2021Enrolled44ConditionsHereditary AngioedemaArmsFactor XIIa antagonist monoclonal antibody, Placebo
NCT04656418 phase3completednot on this map

A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy and Safety of Subcutaneous Administration of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema

TypeinterventionalSponsorCSL BehringRan2021 to 2022Enrolled64ConditionsHereditary AngioedemaArmsCSL312, Placebo
NCT04739059 phase3completednot on this map

An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema

TypeinterventionalSponsorCSL BehringRan2021 to 2025Enrolled171ConditionsHereditary AngioedemaArmsCSL312
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Timothy J CraigAllergy, Asthma and Immunology, Departments of Medicine, Pediatrics and Biomedical Sciences, Pennsylvania State University, Hershey, PA, USA. tcraig@pennstatehealth.psu.edu.ORCID http://orcid.org/0000-0002-7774-4855
Mar GuilarteAllergy Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Barcelona, Spain.ORCID http://orcid.org/0000-0001-7242-9584
Huamin Henry LiInstitute for Asthma and Allergy, Chevy Chase, MD, USA.ORCID http://orcid.org/0000-0001-5587-968X
John AndersonAllerVie Clinical Research, Birmingham, AL, USA.ORCID http://orcid.org/0000-0003-3578-8064
Inmaculada Martinez SaguerHemophilia Center Rhein-Main, Frankfurt, Germany.
Joshua S JacobsAllergy & Asthma Clinical Research, Walnut Creek, CA, USA.
Raffi TachdjianDivision of Allergy and Clinical Immunology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-5387-0013
Henriette FarkasHungarian Angioedema Center of Reference and Excellence, Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary.ORCID http://orcid.org/0000-0003-2929-1721
William H YangOttawa Allergy Research Corporation, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
Isao OhsawaDepartment of Nephrology, Saiyu Soka Hospital, Saitama, Japan.
Roman HaklDepartment of Clinical Immunology and Allergology, St. Anne's University Hospital in Brno, Brno, Czech Republic.ORCID http://orcid.org/0000-0002-1930-4755
Maressa PollenCSL Behring, King of Prussia, PA, USA.
Ingo PragstCSL Innovation GmbH, Marburg, Germany.ORCID http://orcid.org/0000-0002-1259-5422
John-Philip LawoCSL Innovation GmbH, Marburg, Germany.
Harsha ShettyCSL Behring, King of Prussia, PA, USA.
Chiara NenciCSL Behring AG, Bern, Switzerland.
Markus MagerlInstitute of Allergology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt‑Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0001-9218-5468

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionGaradacimab (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.

methodsThe 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.

resultsAt 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]).

conclusionThese 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 registrationClinicalTrials.gov identifiers, NCT03712228, NCT04656418, NCT04739059.

Indexed as

Angioedemas, HereditaryAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAdolescentAdultClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicFemaleHumansMaleMiddle AgedMulticenter Studies as TopicRandomized Controlled Trials as TopicTreatment OutcomeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedgaradacimabGaradacimabHereditary angioedemaLong-term efficacyLong-term prophylaxisLong-term safety

Identifiers

PMID42268494
PMCPMC13499818

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.