AstraZeneca's Calquence Fails to Meet Primary Endpoint in Phase II CALAVI Trials for COVID-19

Compiled by Fan Dongdong

Recently, another drug failed to improve the condition of COVID-19 patients in clinical trials. AstraZeneca recently reported that the Phase II CALAVI trial of Calquence (acalabrutinib) in hospitalized COVID-19 patients with respiratory symptoms did not meet its primary efficacy endpoint. The trial results showed that the drug was not superior to supportive care in improving patient survival or reducing respiratory failure.

Calquence is a selective Bruton’s tyrosine kinase (BTK) inhibitor, originally developed by Acerta Pharma. In 2016, AstraZeneca acquired the drug through acquisition. Currently, AstraZeneca and Acerta are investigating its efficacy in various B-cell hematologic malignancies. Previously, Calquence received approval for adult patients with mantle cell lymphoma (MCL) who have received at least one prior cancer therapy, as well as for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

BTK inhibitors can help suppress autoimmune diseases. In patients with more severe cases of COVID-19, their symptoms are considered to be immune system responses, such as cytokine storm. The purpose of the trial was to test whether Calquence, which can inhibit certain aspects of the immune system, is effective in controlling COVID-19 symptoms. The CALAVI Phase II trial compared the efficacy of Calquence combined with best supportive care (BSC) versus BSC alone. Participants were randomized in a 1:1 ratio, and all enrolled patients were hospitalized but not on mechanical ventilation or admitted to the intensive care unit. The trial was conducted simultaneously in the United States (CALAVI US) and several other countries (CALAVI), with the primary endpoint being respiratory failure or death. The results showed that the safety and tolerability profile of Calquence was consistent with previous trial data.

Jose Baselga, Executive Vice President of Oncology R&D at AstraZeneca, stated, “Since the beginning of this year, AstraZeneca has been doing everything possible to respond to COVID-19, including investigating existing medicines as potential treatments. The CALAVI trial was initiated based on preclinical and early clinical evidence, with prior data suggesting that Calquence could mitigate the heightened inflammatory immune response in patients hospitalized for respiratory symptoms due to COVID-19 and improve clinical outcomes. Although the results of the CALAVI trial are disappointing, we remain committed to advancing scientific progress to help patients confront this unprecedented global pandemic, including through our collaborative clinical trials of a coronavirus vaccine with the University of Oxford.”

According to ClinicalTrials.gov, a Phase 1 trial of the drug is still enrolling patients. Currently, the collaboration between AstraZeneca and the University of Oxford ranks third in the US and European COVID-19 vaccine development programs, trailing only Pfizer with BioNTech and Moderna. This week, Pfizer announced that its COVID-19 mRNA vaccine, co-developed with the German biotechnology company BioNTech, demonstrated 90% efficacy in preventing viral infection. The companies expect to apply for Emergency Use Authorization (EUA) by the end of November and begin distribution and administration by the end of the year. Meanwhile, Moderna anticipates receiving data reports on its vaccine program by the end of this month.

Compared with Calquence, another of AstraZeneca’s products has progressed more smoothly. In October, AstraZeneca received $486 million in funding from the U.S. government to support and advance two Phase 3 clinical trials of its anti-SARS-CoV-2 antibody cocktail therapy, AZD7442. The company stated that it expects to distribute approximately 100,000 doses to high-risk populations by the end of this year. The drug employs half-life extension technology, which AstraZeneca says can provide protection against viral infection for up to 12 months.

References:

1、AstraZeneca's Calquence Fails Pair of Phase II COVID-19 Trials

2、AstraZeneca's Calquence fails COVID-19 study, joining the list of repurposed meds that have fallen short