Berotralstat

Review

Berotralstat

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In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

2024 Jun 20.

PMID: 39047138
Bookshelf ID: NBK605175

Free Books & Documents

Review

Berotralstat

No authors listed.

Free Books & Documents

In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

2024 Jun 20.

PMID: 39047138
Bookshelf ID: NBK605175

Excerpt

Berotralstat is a small molecule inhibitor of plasma kallikrein that is used to prevent acute attacks of hereditary angioedema (HAE) in adults and children 12 years of age or older. Berotralstat has been linked to occasional mild-to-moderate elevations in serum aminotransferase levels during therapy but has not been implicated in instances of clinically apparent liver injury with symptoms or jaundice.

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1. FDA. Integrated Review. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000M...(FDA Summary of the data on the safety and efficacy of berotralstat submitted in support of the application for approval as means of prevention of acute attacks of hereditary angioedema [HAE], mentions that ALT elevations were more frequent with placebo [10%] than berotralstat [2.4% to 5.1%], although one patient on the drug developed ALT elevations of above 5 times the upper limit of normal [ULN] and discontinued treatment with prompt resolution; no serious hepatic adverse events or liver injury with jaundice).
1. Aygören-Pürsün E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, et al. Oral plasma kallikrein inhibitor for prophylaxis in hereditary angioedema. N Engl J Med. 2018;379:352-362.(Among 77 patients with HAE treated with berotralstat [62.5, 125, 250, or 350 mg] or placebo once daily for 28 days, acute HAE attacks were reduced by 47% to 75% by the higher doses, but adverse events also increased with dose including mild-to-moderate ALT elevations [but without symptoms or jaundice] of 7% and 11% at the two highest doses). - PubMed
1. Lee A. Berotralstat: first approval. Drugs. 2021;81:405-409.(Summary of the mechanism of action, history of development, pharmacology, clinical efficacy, and safety of berotralstat shortly after its approval in the US as a means of prevention of attacks of HAE, does not mention ALT elevations or hepatotoxicity). - PubMed
1. Zuraw B, Lumry WR, Johnston DT, Aygören-Pürsün E, Banerji A, Bernstein JA, Christiansen SC, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021;148:164-172.e9.(Among 120 patients with HAE [ages 23 years or older] treated with berotralstat [110 or 150 mg] or placebo once daily for 24 weeks, the acute attack rate was lower with berotralstat [1.7 and 1.3 vs 2.4 per month] while adverse events more frequent with drug included abdominal pain [10%-23% vs 10%], vomiting [10%-15% vs 3%], diarrhea [10%-15% vs 0%] and back pain [2%-10% vs 3%], and one patient on 150 mg daily developed an asymptomatic rise in ALT above 10 times ULN that resolved on discontinuation). - PubMed
1. Wedner HJ, Aygören-Pürsün E, Bernstein J, Craig T, Gower R, Jacobs JS, Johnston DT, et al. Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of APeX-2 through 48 weeks (Part 2). J Allergy Clin Immunol Pract. 2021;9:2305-2314.e4.(Among 108 patients with HAE participating in a 24-week controlled trial [Zuraw 2021] treated with open label berotralstat [110 or 150 mg daily] for another 24 weeks, the monthly acute attack rate continued to decline particularly with the higher dose, while adverse events were largely mild-to-moderate gastrointestinal complaints; no mention of ALT elevations or hepatotoxicity). - PubMed

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[1] FDA. Integrated Review. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000M...(FDA Summary of the data on the safety and efficacy of berotralstat submitted in support of the application for approval as means of prevention of acute attacks of hereditary angioedema [HAE], mentions that ALT elevations were more frequent with placebo [10%] than berotralstat [2.4% to 5.1%], although one patient on the drug developed ALT elevations of above 5 times the upper limit of normal [ULN] and discontinued treatment with prompt resolution; no serious hepatic adverse events or liver injury with jaundice).

[2] FDA. Integrated Review. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/214094Orig1s000M...(FDA Summary of the data on the safety and efficacy of berotralstat submitted in support of the application for approval as means of prevention of acute attacks of hereditary angioedema [HAE], mentions that ALT elevations were more frequent with placebo [10%] than berotralstat [2.4% to 5.1%], although one patient on the drug developed ALT elevations of above 5 times the upper limit of normal [ULN] and discontinued treatment with prompt resolution; no serious hepatic adverse events or liver injury with jaundice).

[3] Aygören-Pürsün E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, et al. Oral plasma kallikrein inhibitor for prophylaxis in hereditary angioedema. N Engl J Med. 2018;379:352-362.(Among 77 patients with HAE treated with berotralstat [62.5, 125, 250, or 350 mg] or placebo once daily for 28 days, acute HAE attacks were reduced by 47% to 75% by the higher doses, but adverse events also increased with dose including mild-to-moderate ALT elevations [but without symptoms or jaundice] of 7% and 11% at the two highest doses). - PubMed

[4] Aygören-Pürsün E, Bygum A, Grivcheva-Panovska V, Magerl M, Graff J, Steiner UC, Fain O, et al. Oral plasma kallikrein inhibitor for prophylaxis in hereditary angioedema. N Engl J Med. 2018;379:352-362.(Among 77 patients with HAE treated with berotralstat [62.5, 125, 250, or 350 mg] or placebo once daily for 28 days, acute HAE attacks were reduced by 47% to 75% by the higher doses, but adverse events also increased with dose including mild-to-moderate ALT elevations [but without symptoms or jaundice] of 7% and 11% at the two highest doses). - PubMed

[5] Lee A. Berotralstat: first approval. Drugs. 2021;81:405-409.(Summary of the mechanism of action, history of development, pharmacology, clinical efficacy, and safety of berotralstat shortly after its approval in the US as a means of prevention of attacks of HAE, does not mention ALT elevations or hepatotoxicity). - PubMed

[6] Lee A. Berotralstat: first approval. Drugs. 2021;81:405-409.(Summary of the mechanism of action, history of development, pharmacology, clinical efficacy, and safety of berotralstat shortly after its approval in the US as a means of prevention of attacks of HAE, does not mention ALT elevations or hepatotoxicity). - PubMed

[7] Zuraw B, Lumry WR, Johnston DT, Aygören-Pürsün E, Banerji A, Bernstein JA, Christiansen SC, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021;148:164-172.e9.(Among 120 patients with HAE [ages 23 years or older] treated with berotralstat [110 or 150 mg] or placebo once daily for 24 weeks, the acute attack rate was lower with berotralstat [1.7 and 1.3 vs 2.4 per month] while adverse events more frequent with drug included abdominal pain [10%-23% vs 10%], vomiting [10%-15% vs 3%], diarrhea [10%-15% vs 0%] and back pain [2%-10% vs 3%], and one patient on 150 mg daily developed an asymptomatic rise in ALT above 10 times ULN that resolved on discontinuation). - PubMed

[8] Zuraw B, Lumry WR, Johnston DT, Aygören-Pürsün E, Banerji A, Bernstein JA, Christiansen SC, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. J Allergy Clin Immunol. 2021;148:164-172.e9.(Among 120 patients with HAE [ages 23 years or older] treated with berotralstat [110 or 150 mg] or placebo once daily for 24 weeks, the acute attack rate was lower with berotralstat [1.7 and 1.3 vs 2.4 per month] while adverse events more frequent with drug included abdominal pain [10%-23% vs 10%], vomiting [10%-15% vs 3%], diarrhea [10%-15% vs 0%] and back pain [2%-10% vs 3%], and one patient on 150 mg daily developed an asymptomatic rise in ALT above 10 times ULN that resolved on discontinuation). - PubMed

[9] Wedner HJ, Aygören-Pürsün E, Bernstein J, Craig T, Gower R, Jacobs JS, Johnston DT, et al. Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of APeX-2 through 48 weeks (Part 2). J Allergy Clin Immunol Pract. 2021;9:2305-2314.e4.(Among 108 patients with HAE participating in a 24-week controlled trial [Zuraw 2021] treated with open label berotralstat [110 or 150 mg daily] for another 24 weeks, the monthly acute attack rate continued to decline particularly with the higher dose, while adverse events were largely mild-to-moderate gastrointestinal complaints; no mention of ALT elevations or hepatotoxicity). - PubMed

[10] Wedner HJ, Aygören-Pürsün E, Bernstein J, Craig T, Gower R, Jacobs JS, Johnston DT, et al. Randomized trial of the efficacy and safety of berotralstat (BCX7353) as an oral prophylactic therapy for hereditary angioedema: results of APeX-2 through 48 weeks (Part 2). J Allergy Clin Immunol Pract. 2021;9:2305-2314.e4.(Among 108 patients with HAE participating in a 24-week controlled trial [Zuraw 2021] treated with open label berotralstat [110 or 150 mg daily] for another 24 weeks, the monthly acute attack rate continued to decline particularly with the higher dose, while adverse events were largely mild-to-moderate gastrointestinal complaints; no mention of ALT elevations or hepatotoxicity). - PubMed

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