Oral once-daily berotralstat for the prevention of hereditary
angioedema attacks: A randomized, double-blind,
placebo-controlled phase 3 trial

J 2021

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

ZURAW, B., W. R. LUMRY, D. T. JOHNSTON, E. AYGOREN-PURSUN, A. BANERJI et. al.

Basic information

Original name

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

Authors

ZURAW, B., W. R. LUMRY, D. T. JOHNSTON, E. AYGOREN-PURSUN, A. BANERJI, J. A. BERNSTEIN, S. C. CHRISTIANSEN, J. S. JACOBS, K. V. SITZ, R. G. GOWER, R. GAGNON, H. J. WEDNER, T. KINACIYAN, Roman HAKL (203 Czech Republic, belonging to the institution), Jana HANZLIKOVA (203 Czech Republic), J. T. ANDERSON, D. L. MCNEIL, S. B. FRITZ, W. H. YANG, R. TACHDJIAN, P. J. BUSSE, T. J. CRAIG, H. H. LI, H. FARKAS, J. M. BEST, D. CLEMONS, M. CORNPROPST, S. M. DOBO, H. A. IOCCA, D. KARGL, E. NAGY, S. C. MURRAY, P. COLLIS, W. P. SHERIDAN, M. MAURER and M. A. RIEDL

Edition

Journal of allergy and clinical immunology, New York, Mosby-Elsevier, 2021, 0091-6749

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30225 Allergy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.290

RIV identification code

RIV/00216224:14110/21:00122116

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.jaci.2020.10.015

UT WoS

000669906700024

Keywords in English

BCX7353; berotralstat; C1 inhibitor; efficacy; HAE; hereditary angioedema; kallikrein inhibitor; long-term prophylaxis; prophylaxis; safety

Abstract

V originále

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.

Citovat

ZURAW, B., W. R. LUMRY, D. T. JOHNSTON, E. AYGOREN-PURSUN, A. BANERJI, J. A. BERNSTEIN, S. C. CHRISTIANSEN, J. S. JACOBS, K. V. SITZ, R. G. GOWER, R. GAGNON, H. J. WEDNER, T. KINACIYAN, Roman HAKL, Jana HANZLIKOVA, J. T. ANDERSON, D. L. MCNEIL, S. B. FRITZ, W. H. YANG, R. TACHDJIAN, P. J. BUSSE, T. J. CRAIG, H. H. LI, H. FARKAS, J. M. BEST, D. CLEMONS, M. CORNPROPST, S. M. DOBO, H. A. IOCCA, D. KARGL, E. NAGY, S. C. MURRAY, P. COLLIS, W. P. SHERIDAN, M. MAURER and M. A. RIEDL. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. Journal of allergy and clinical immunology. New York: Mosby-Elsevier, 2021, vol. 148, No 1, p. "164"-"172.e9", 18 pp. ISSN 0091-6749. Available from: https://dx.doi.org/10.1016/j.jaci.2020.10.015.

@article{1786780,
   author = {Zuraw, B. and Lumry, W. R. and Johnston, D. T. and AygorenandPursun, E. and Banerji, A. and Bernstein, J. A. and Christiansen, S. C. and Jacobs, J. S. and Sitz, K. V. and Gower, R. G. and Gagnon, R. and Wedner, H. J. and Kinaciyan, T. and Hakl, Roman and Hanzlikova, Jana and Anderson, J. T. and McNeil, D. L. and Fritz, S. B. and Yang, W. H. and Tachdjian, R. and Busse, P. J. and Craig, T. J. and Li, H. H. and Farkas, H. and Best, J. M. and Clemons, D. and Cornpropst, M. and Dobo, S. M. and Iocca, H. A. and Kargl, D. and Nagy, E. and Murray, S. C. and Collis, P. and Sheridan, W. P. and Maurer, M. and Riedl, M. A.},
   article_location = {New York},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.jaci.2020.10.015},
   keywords = {BCX7353; berotralstat; C1 inhibitor; efficacy; HAE; hereditary angioedema; kallikrein inhibitor; long-term prophylaxis; prophylaxis; safety},
   language = {eng},
   issn = {0091-6749},
   journal = {Journal of allergy and clinical immunology},
   title = {Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial},
   url = {https://www.sciencedirect.com/science/article/pii/S0091674920314846?via%3Dihub},
   volume = {148},
   year = {2021}
}

TY  - JOUR
ID  - 1786780
AU  - Zuraw, B. - Lumry, W. R. - Johnston, D. T. - Aygoren-Pursun, E. - Banerji, A. - Bernstein, J. A. - Christiansen, S. C. - Jacobs, J. S. - Sitz, K. V. - Gower, R. G. - Gagnon, R. - Wedner, H. J. - Kinaciyan, T. - Hakl, Roman - Hanzlikova, Jana - Anderson, J. T. - McNeil, D. L. - Fritz, S. B. - Yang, W. H. - Tachdjian, R. - Busse, P. J. - Craig, T. J. - Li, H. H. - Farkas, H. - Best, J. M. - Clemons, D. - Cornpropst, M. - Dobo, S. M. - Iocca, H. A. - Kargl, D. - Nagy, E. - Murray, S. C. - Collis, P. - Sheridan, W. P. - Maurer, M. - Riedl, M. A.
PY  - 2021
TI  - Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial
JF  - Journal of allergy and clinical immunology
VL  - 148
IS  - 1
SP  - "164"-"172.e9"
EP  - "164"-"172.e9"
PB  - Mosby-Elsevier
SN  - 00916749
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
UR  - https://www.sciencedirect.com/science/article/pii/S0091674920314846?via%3Dihub
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.
ER  -

ZURAW, B., W. R. LUMRY, D. T. JOHNSTON, E. AYGOREN-PURSUN, A. BANERJI, J. A. BERNSTEIN, S. C. CHRISTIANSEN, J. S. JACOBS, K. V. SITZ, R. G. GOWER, R. GAGNON, H. J. WEDNER, T. KINACIYAN, Roman HAKL, Jana HANZLIKOVA, J. T. ANDERSON, D. L. MCNEIL, S. B. FRITZ, W. H. YANG, R. TACHDJIAN, P. J. BUSSE, T. J. CRAIG, H. H. LI, H. FARKAS, J. M. BEST, D. CLEMONS, M. CORNPROPST, S. M. DOBO, H. A. IOCCA, D. KARGL, E. NAGY, S. C. MURRAY, P. COLLIS, W. P. SHERIDAN, M. MAURER and M. A. RIEDL. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. \textit{Journal of allergy and clinical immunology}. New York: Mosby-Elsevier, 2021, vol.~148, No~1, p.~''164''-''172.e9'', 18 pp. ISSN~0091-6749. Available from: https://dx.doi.org/10.1016/j.jaci.2020.10.015.

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