Clinical Improvement Found After Administration of Acalabrutinib for Patients with COVID-19

June 8, 2020

A recent study, sparking further trials for investigation, saw improved clinical outcomes and reduced markers of inflammation for patients with severe COVID-19 after treatment with acalabrutinib, a selective BTK inhibitor.

Clinical outcomes improved and reduced markers of inflammation were seen after administration of acalabrutinib (Calquence) for patients with severe coronavirus disease 2019 (COVID-19), according to results of a study published in Science Immunology.

More, oxygen requirements among the patients decreased, with ongoing global trials in motion to confirm the findings.

“The science supporting investigation of the use of Calquence in patients with severe COVID-19 is strong,” José Baselga, executive vice president, oncology R&D, said in a press release. “The encouraging preliminary data in this case series has informed the initiation of global phase 2 trials, notably the CALAVI program. We look forward to completing recruitment and obtaining data in these trials as soon as possible to further our understanding of what this potential treatment could mean for patients.”

The data was collected from a peer-review case series examining 19 hospitalized patients with severe respiratory illness linked to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The series is a collaboration from investigators across the United States, led by Wyndham Wilson, MD, PhD, and Louis Staudt, MD, PhD, of the National Cancer Institute of the National Institutes of Health.

A “cytokine storm” or virus-induced hyperimmune response is thought to be a major pathogenic mechanism of respiratory illness in this cohort. More, the evidence suggests that dysregulated BTK-dependent lung macrophage signaling works with the cytokine storm to play a role in the SARS-CoV-2 virus.

The CALAVI program contains 2 randomized, open-label, multicenter, global trials that are intended to evaluate the safety and efficacy of acalabrutinib in conjunction with best supportive care versus best supportive care alone for patients hospitalized with COVID-19 complications. The trials focus on acalabrutinib in combination with current best supportive care for patients hospitalized for COVID-19 but who are not on ventilators.

Acalabrutinib is a next-generation, selective BTK inhibitor which binds covalently to BTK, inhibiting its activity. While its currently not approved to treat patients with SARS-CoV-2, the BTK inhibitor is approved in the United States for the treatment of some hematological malignancies.

While BTK is a key regulator of multiple cytokines and chemokines, BTK inhibition works to reduce the production of these cytokines, making it a particularly promising strategy to reduce the respiratory complications caused by COVID-19.

The COVID-19 disease is a new pandemic caused by the SARS-CoV-2 virus. While some cases of COVID-19 require swift care and hospitalization due to pneumonia, about 80% of cases are mild respiratory illnesses.

Reference:

Calquence showed promising clinical improvement in majority of 19 hospitalised COVID-19 patients [news release]. Published June 5, 2020. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/calquence-showed-promising-clinical-improvement-in-majority-of-19-hospitalised-covid-19-patients.html. Accessed June 8, 2020.