Candidate: Calquence® (acalabrutinib)

Type: Next-generation, highly selective Bruton’s tyrosine kinase (BTK) inhibitor indicated for Mantle cell lymphoma patients who have received at least one prior therapy, and chronic lymphocytic leukemia or small lymphocytic leukemia.

Status: The NIH on June 5 said the design of the Phase II CALAVI trial (NCT04346199)—a randomized, global clinical trial to assess Calquence as a treatment for cytokine storm associated with COVID-19 infection in severely ill patients—was informed by a clinical study whose early data suggested that blocking the BTK protein provided clinical benefit to a small group of patients with severe COVID-19. In a study published June 5 in Science Immunology, the investigators observed that off-label use of Calquence was associated with reduced respiratory distress and a reduction in the overactive immune response in most of the treated patients.

The study evaluated 19 patients with a confirmed COVID-19 diagnosis that required hospitalization, as well as with low blood-oxygen levels and evidence of inflammation. Of the 19 patients, 11 had been receiving supplemental oxygen for a median of two days, and eight others had been on ventilators for a median of 1.5 (range 1-22) days.The study was led by researchers in the Center for Cancer Research at the National Cancer Institute (NCI), in collaboration with researchers from the National Institute of Allergy and Infectious Diseases (NIAID), both part of the National Institutes of Health, as well as the U.S. Department of Defense’s Walter Reed National Military Medical Center, and four other hospitals nationally.

In April, AstraZeneca disclosed plans to begin CALAVI, based on early clinical data with Calquence. According to the company, that data showed that a decrease in inflammation caused by BTK inhibition appeared to reduce the severity of COVID-19-induced respiratory distress in a small number of patients at Walter Reed.

The trial—two arms totaling 428 patients—aims to evaluate the efficacy and safety of adding Calquence to best supportive care (BSC); the primary endpoint measures the use of assisted ventilation or death.

COVID-19: 200 Candidates and Counting

To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types: