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

Jose Baselga, EVP and President, Research & Development Oncology at AstraZeneca. Photo courtesy of AstraZeneca. 

Yet another drug has failed to improve conditions for COVID-19 patients in a clinical trial. AstraZeneca reported that the CALAVI Phase II trials of Calquence (acalabrutinib) in hospitalized patients with respiratory symptoms of COVID-19 failed to meet the trials’ primary efficacy endpoint.

Calquence is the company’s next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK), which is otherwise being developed for multiple B-cell blood cancers by AstraZeneca and Acerta Pharma. Calquence is approved for use in adults with mantle cell lymphoma (MCL) who have received at least one previous treatment for their cancer, or adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Bruton’s tyrosine kinase (BTK) inhibitors are used to suppress autoimmune diseases. In COVID-19 patients with severe symptoms that include pneumonia, their symptoms are believed to be an immune system reaction, such as the cytokine storm. The goal was to test if Calquence, which suppresses some of the immune system, can be effective in controlling that aspect of COVID-19.

The CALAVI Phase II program is made up of two trials of Calquence with best supportive care (BSC) compared to BSC alone in patients hospitalized with respiratory complications of COVID-19. Patients were randomized 1:1. The patients were hospitalized, but not on mechanical ventilation and were not in the intensive care unit. The primary endpoint measured respiratory failure or death. The trial was run in the U.S. (CALAVI US) and in several other countries (CALAVI).

“Since the beginning of the year, AstraZeneca has been committed to doing everything we can to respond to COVID-19, including investigating existing medicines as potential treatments,” said Jose Baselga, AstraZeneca’s executive vice president, Oncology R&D. “The CALAVI trials were launched based on preclinical and early clinical evidence that Calquence could decrease the hyperinflammatory immune response and improve clinical outcomes in patients hospitalized with respiratory symptoms of COVID-19. While the CALAVI results are disappointing, we remain committed to advancing science that helps patients during this unprecedented global pandemic, including clinical trials for the AstraZeneca Oxford coronavirus vaccine and our long-acting antibody combination.”

The AstraZeneca-University of Oxford COVID-19 vaccine program is running about third in U.S. and European development programs, behind the Pfizer-BioNTech group and Moderna. Earlier this week, Pfizer and BioNTech reported that their COVID-19 vaccine is about 90% effective in the first interim analysis of data from the Phase III clinical trial. Barring any unexpected glitches, they will likely apply for an emergency use authorization (EUA) by the end of November and begin distribution before the end of the year.

Moderna has indicated they are projected to have data to report by the end of the month on their vaccine program. They said they needed 53 patients in the study to be diagnosed with COVID-19, and the trial hit that figure yesterday. At this time the data is blinded so they don’t know yet if the sick patients received the vaccine or the placebo, but they are preparing the data for the Data and Safety Monitoring Board.

Last week, AstraZeneca reported they expected data on their vaccine program within the next eight weeks, somewhat dependent upon the rate of infection within the communities where the trials are being conducted. That would place the interim data readout somewhere around Christmas. If positive, an EUA application might be possible by the end of the year or sometime in January.

In mid-October, AstraZeneca inked a $486 million deal with the U.S. government to fund two Phase III trials of its anti-SARS-CoV-2 antibody cocktail, AZD7442. AstraZeneca’s approach uses half-life extending technologies, and the company believes it could prevent infection against the virus for up to 12 months. The deal secured up to 100,000 doses for the U.S. supply by the end of the year, with an option to buy up to 1 million doses in 2021.