Systematic Literature Review of Recombinant C1 Esterase Inhibitor (rhC1-INH) and Other Products for the On-Demand Treatment of Hereditary Angioedema Attacks
Author(s)
Mark Davis-Lorton, MD1, Raffi Tachdjian, MD, MPH2, Paranjoy Saharia, MSc3, Sakshi Jindal, MPharm, MPharmacology3, Nami Park, PharmD4, Joseph Harper, PharmD4, Anurag Relan, MD4, Amanda Harrington, MS, PhD4, Nihal Narsipur, MPH, PharmD4, John Anderson, MD5.
1ENT and Allergy Associates, Tarrytown, NY, USA, 2University of California, Los Angeles, Los Angeles, CA, USA, 3Lumanity, Gurugram, India, 4Pharming Healthcare, Inc., Warren, NJ, USA, 5AllerVie Health, Birmingham, AL, USA.
1ENT and Allergy Associates, Tarrytown, NY, USA, 2University of California, Los Angeles, Los Angeles, CA, USA, 3Lumanity, Gurugram, India, 4Pharming Healthcare, Inc., Warren, NJ, USA, 5AllerVie Health, Birmingham, AL, USA.
Presentation Documents
OBJECTIVES: Hereditary angioedema (HAE) is a rare genetic disorder affecting approximately 1 in 50,000 people worldwide. Through a systematic literature review (SLR), this study sought to better understand clinical trial designs, populations, and outcomes for on-demand HAE treatments.
METHODS: An SLR was conducted via searches in PubMed®, Embase®, and the Cochrane Library databases (inception-October 2024) and of proceedings from AAAAI, EAACI, and ACAAI congresses (2022-2024), and by handsearching (eg, ClinicalTrials.gov, accessdata.fda.gov, and trial journal sites [eg, NEJM.org]); PRISMA guidelines and PRESS checklist were followed. Eligible publications included phases 2, 3, and 4 randomized controlled trials (RCTs) and open-label extension (OLE) studies assessing HAE attacks in patients aged ≥12 years with the following interventions: Ruconest® (conestat alfa), Firazyr® (icatibant), Kalbitor® (ecallantide), sebetralstat (KVD900), and Berinert (C1 esterase inhibitor, human). Characteristics of patients, attacks, and study design were assessed for qualitative comparability across studies.
RESULTS: Twenty-two studies (12 RCTs, 10 OLEs) were included in the SLR, and 101 records were evaluated. Trials (n=number of unique retrievable records) included for each intervention were as follows: Ruconest®, 3 RCTs (n=18) and 3 OLEs (n=5); Kalbitor®, 3 RCTs (n=19) and 2 OLEs (n=0); Firazyr®, 3 RCTs (n=15) and 3 OLEs (n=2); Berinert, 1 RCT (n=7) and 1 OLE (n=6); and sebetralstat, 2 RCTs (n=28) and 1 OLE (n=1). Individual records may have reported data for both RCTs and OLEs; however, they were preferentially counted within the RCT tally.
CONCLUSIONS: The study populations and end point definitions used in clinical trials assessing acute HAE treatments have changed over time. Key study differences included route of administration, trial setting, time of treatment, attack severity at enrollment, attack location, redosing and rescue therapy criteria, patient-reported outcome assessments, and outcome definitions. Further investigation is warranted to evaluate these differences and determine whether they affected study outcomes.
METHODS: An SLR was conducted via searches in PubMed®, Embase®, and the Cochrane Library databases (inception-October 2024) and of proceedings from AAAAI, EAACI, and ACAAI congresses (2022-2024), and by handsearching (eg, ClinicalTrials.gov, accessdata.fda.gov, and trial journal sites [eg, NEJM.org]); PRISMA guidelines and PRESS checklist were followed. Eligible publications included phases 2, 3, and 4 randomized controlled trials (RCTs) and open-label extension (OLE) studies assessing HAE attacks in patients aged ≥12 years with the following interventions: Ruconest® (conestat alfa), Firazyr® (icatibant), Kalbitor® (ecallantide), sebetralstat (KVD900), and Berinert (C1 esterase inhibitor, human). Characteristics of patients, attacks, and study design were assessed for qualitative comparability across studies.
RESULTS: Twenty-two studies (12 RCTs, 10 OLEs) were included in the SLR, and 101 records were evaluated. Trials (n=number of unique retrievable records) included for each intervention were as follows: Ruconest®, 3 RCTs (n=18) and 3 OLEs (n=5); Kalbitor®, 3 RCTs (n=19) and 2 OLEs (n=0); Firazyr®, 3 RCTs (n=15) and 3 OLEs (n=2); Berinert, 1 RCT (n=7) and 1 OLE (n=6); and sebetralstat, 2 RCTs (n=28) and 1 OLE (n=1). Individual records may have reported data for both RCTs and OLEs; however, they were preferentially counted within the RCT tally.
CONCLUSIONS: The study populations and end point definitions used in clinical trials assessing acute HAE treatments have changed over time. Key study differences included route of administration, trial setting, time of treatment, attack severity at enrollment, attack location, redosing and rescue therapy criteria, patient-reported outcome assessments, and outcome definitions. Further investigation is warranted to evaluate these differences and determine whether they affected study outcomes.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO31
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Clinician Reported Outcomes
Disease
SDC: Rare & Orphan Diseases