A phase III trial has revealed that fostamatinib (Tavalisse), a spleen tyrosine kinase inhibitor, did not improve outcomes in adult patients hospitalized with COVID-19 and hypoxemia. The study, published in JAMA Network Open, contradicts earlier trials that suggested potential efficacy of fostamatinib in treating COVID-19 patients.
The trial focused on patients who developed new hypoxemia during hospitalization or experienced an increased oxygen requirement. The primary outcome measured was oxygen-free days, a composite of survival and the absence of the need for supplemental oxygen. This endpoint was chosen based on its importance to both investigators and patients, reflecting the desire to return to normal activities without oxygen dependence.
Trial Design and Patient Population
The study design mirrored characteristics of previous phase II and phase III trials that had indicated fostamatinib's potential benefits in COVID-19. However, the results showed that fostamatinib did not significantly improve oxygen-free days in the studied patient population. This was unexpected, given the earlier trials' suggestions that fostamatinib could improve oxygen requirements, particularly in severely ill patients requiring high levels of oxygen.
Sean P. Collins, MD, MSc, of Vanderbilt University Medical Center, noted that the characteristics of COVID-19 as a disease had changed significantly by the time this trial was conducted. "COVID was just a much different disease at the end of the pandemic compared to the beginning," Collins stated. Key differences included higher vaccination rates, older patient age, and a greater prevalence of comorbidities, such as underlying lung disease. In contrast to the beginning of the pandemic, when young, healthy individuals were severely affected, the later stages saw breakthrough infections in vaccinated patients with pre-existing conditions.
Implications and Future Research
The trial's findings suggest that the evolving nature of COVID-19 and changes in patient demographics may have influenced the outcomes. Further mechanistic substudies are planned to differentiate between lung injury caused by COVID-19 infection and exacerbations of chronic underlying lung disease. These studies aim to provide a more detailed understanding of the factors contributing to respiratory distress in COVID-19 patients and may offer insights into more targeted treatment strategies.
