TY  - JOUR
A1  - Zuraw, Bruce L.
A1  - Lumry, William R.
A1  - Johnston, Douglas T.
A1  - Aygören-Pürsün, Emel
A1  - Banerji, Aleena
A1  - Bernstein, Jonathan A.
A1  - Christiansen, Sandra C.
A1  - Jacobs, Joshua S.
A1  - Sitz, Karl V.
A1  - Gower, Richard G.
A1  - Gagnon, Remi
A1  - Wedner, H. James
A1  - Kinaciyan, Tamar
A1  - Hakl, Roman
A1  - Hanzlíková, Jana
A1  - Anderson, John T.
A1  - McNeil, Donald L.
A1  - Fritz, Stephen B.
A1  - Yang, William H.
A1  - Tachdjian, Raffi
A1  - Busse, Paula J.
A1  - Craig, Timothy J.
A1  - Li, H. Henry
A1  - Farkas, Henriette
A1  - Best, Jessica M.
A1  - Clemons, Desiree
A1  - Cornpropst, Melanie
A1  - Dobo, Sylvia M.
A1  - Iocca, Heather A.
A1  - Kargl, Deborah
A1  - Nagy, Eniko
A1  - Murray, Sharon C.
A1  - Collis, Phil
A1  - Sheridan, William P.
A1  - Maurer, Marcus
A1  - Riedl, Marc A.
T1  - Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial
T2  - The journal of allergy and clinical immunology
N2  - Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.
Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).
Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.
Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.
Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
KW  - BCX7353
KW  - berotralstat
KW  - C1 inhibitor
KW  - efficacy
KW  - HAE
KW  - hereditary angioedema
KW  - kallikrein inhibitor
KW  - long-term prophylaxis
KW  - prophylaxis
KW  - safety
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63104
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-631049
SN  - 1097-6825
N1  - This study was funded by BioCryst Pharmaceuticals, Inc. At Harvard Medical School, the study was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award UL1 TR001102).
VL  - 148
IS  - 1
SP  - 164
EP  - 172.e9
PB  - Elsevier
CY  - Amsterdam [u.a.]
ER  -