Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: the OPUS-2 study.

Riedl, Marc A and Aygören-Pürsün, Emel and Baker, James and Farkas, Henriette and Anderson, John and Bernstein, Jonathan A and Bouillet, Laurence and Busse, Paula and Manning, Michael and Magerl, Markus and Gompels, Mark and Huissoon, Aarnoud P and Longhurst, Hillary and Lumry, William and Ritchie, Bruce and Shapiro, Ralph and Soteres, Daniel and Banerji, Aleena and Cancian, Mauro and Johnston, Douglas T and Craig, Timothy J and Launay, David and Li, H Henry and Liebhaber, Myron and Nickel, Timothy and Offenberger, Jacob and Rae, William and Schrijvers, Rik and Triggiani, Massimo and Wedner, H James and Dobo, Sylvia and Cornpropst, Melanie and Clemons, Desiree and Fang, Lei and Collis, Phil and Sheridan, William P and Maurer, Marcus (2018) Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: the OPUS-2 study. Allergy. ISSN 1398-9995. This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

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Official URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/al...

Abstract

BACKGROUND

Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo.

METHODS

OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks.

RESULTS

A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4 and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg and placebo groups respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated.

CONCLUSIONS

Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo. This article is protected by copyright. All rights reserved.

Item Type: Article
Additional Information: This article is available to all HEFT staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects: WD Diseases and disorders of systemic, metabolic or environmental origin
WD Diseases and disorders of systemic, metabolic or environmental origin > WD300 Hypersensitivity. Allergy
WD Diseases and disorders of systemic, metabolic or environmental origin > WD350 Immunologic diseases
Divisions: Planned IP Care > Respiratory Medicine
Related URLs:
Depositing User: Mr Philip O'Reilly
Date Deposited: 04 May 2018 14:35
Last Modified: 04 May 2018 14:35
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1646

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