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Clinical Trial
. 2025 May 30;9(7):vlaf023.
doi: 10.1093/immhor/vlaf023.

Efficacy and safety of acalabrutinib with best supportive care versus best supportive care in patients with COVID-19 requiring hospitalization

Phillip Scheinberg  1 , Matt R Khoshnevis  2 , Philip A Robinson  3 , Alfredo Guerreros  4 , Victor A H Sato  5 , Benedito A L Fonseca  6 , Hans W Prozesky  7 , José Omar Chacón Romero  8 , Laura Fogliatto  9 , Barry R Meisenberg  10 , David J Park  11 , Ashok Gupta  12 , Priti Patel  13 , Danielle M Townsley  12 , Lianqing Zheng  14 , Veerendra Munugalavadla  13
Affiliations
Clinical Trial

Efficacy and safety of acalabrutinib with best supportive care versus best supportive care in patients with COVID-19 requiring hospitalization

Phillip Scheinberg et al. Immunohorizons. .

Abstract

The efficacy and safety of acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, was evaluated in 2 phase 2 studies in hospitalized patients with coronavirus disease 2019 (COVID-19) who received acalabrutinib + best supportive care (BSC) versus BSC alone (Clinicaltrials.gov: NCT04380688 and NCT04346199). The primary endpoint was the percentage of patients alive and free of respiratory failure on day 14 (rest of the world [RoW] study) and day 28 (US study). In the RoW study, 177 patients were randomized (acalabrutinib + BSC: n = 89; BSC: n = 88); in the US study, 62 patients were randomized (acalabrutinib + BSC: n = 31; BSC: n = 31). The percentage of patients who met the primary endpoint was similar in both studies (RoW study: acalabrutinib + BSC: 83.1%, BSC: 90.9%; US study: acalabrutinib + BSC: 80.6%, BSC: 83.9%). No new safety concerns were reported. Overall, no significant clinical benefit of adding acalabrutinib to BSC in patients hospitalized with COVID-19 was observed.

Keywords: COVID-19; acalabrutinib; best supportive care; bruton tyrosine kinase inhibitor; hospitalized patients.

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Conflict of interest statement

M.R.K. has none to disclose.

P.A.R. has none to disclose.

A.G. has none to disclose.

V.A.H.S. has none to disclose.

B.A.L.F. has none to disclose.

H.W.P. has none to disclose.

J.R.C. has none to disclose.

L.F. has none to disclose.

B.R.M. has none to disclose.

D.J.P. has served at a speaker’s bureau for AstraZeneca and CARIS and was provided research funding from Genentech/Roche, BeiGene, Gilead, Novartis, Astellas, Merck, LaNova, BMS, Agenus, Panbela, AstraZeneca, Mirati, and Lisata.

A.G. is an employee and shareholder of AstraZeneca.

P.P. and D.T. were employees and shareholders of AstraZeneca at the time that the study was conducted.

L.Z. was an employee and shareholder of AstraZeneca and stockholder of Gilead Sciences at the time that the study was conducted.

V.M. is an employee and shareholder of AstraZeneca; a family member is an employee and stockholder of Gilead Sciences.

P.S. reports receiving consulting fees or honoraria for lectures, presentations, speakers’ bureaus, and advisory boards from AstraZeneca, Alexion, Novartis, Pfizer, and Roche.

Figures

Figure 1.
Figure 1.
Study design, patient disposition, and endpoints. BID, twice daily; BSC, best supportive care; COVID-19, coronavirus disease 2019; RoW, rest of the world; SARS-CoV-2+, severe acute respiratory syndrome coronavirus 2 positive; SpO2, oxygen saturation; US, United States.
Figure 2.
Figure 2.
Primary endpoint: proportion of patients alive and free of respiratory failure in (A) the RoW study and (B) the US study. BSC, best supportive care; RoW, rest of the world; US, United States.
Figure 3.
Figure 3.
SARS-CoV-2 viral load profile over time in (A) the RoW study and (B) the US study. BSC, best supportive care; RoW, rest of the world; RT-qPCR, real-time quantitative polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; US, United States.
Figure 4.
Figure 4.
SARS-CoV-2 antibody detection in the US study. (A) Detection of antibodies against the SARS-CoV-2 spike, RBD, and nucleocapsid proteins, and (B) detection of total SARS-CoV-2 antibodies. Ab, antibody; BSC, best supportive care; COVID, coronavirus disease 19; N, nucleocapsid; Quant, quantification; RBD, receptor-binding domain; S, spike; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; US, United States.
Figure 5.
Figure 5.
Oxygenation index over time in for (A) acalabrutinib + BSC in the RoW study, (B) BSC alone in the RoW study, (C) acalabrutinib + BSC in the US study, and (D) BSC alone in the US study. Oxygenation index = SpO2/FiO2, where SpO2 is a percentage and FiO2 is a decimal. For patients discharged from hospital prior to day 10, this is the last post-baseline assessment reported. For patients discharged from the hospital on or after day 10, this is the day 10 assessment. BSC, best supportive care; Dis, discontinuation; RoW, rest of the world; US, United States.
Figure 6.
Figure 6.
Levels of inflammatory cytokines over time. BSC, best supportive care; CRP, C-reactive protein; IL-6, interleukin 6; RoW, rest of the world; TNF-α, tumor necrosis factor-alpha; US, United States.
See this image and copyright information in PMC

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