ITP Drug Disappoints in Hospitalized COVID Patients With Hypoxemia

The spleen tyrosine kinase inhibitor fostamatinib (Tavalisse) did not improve outcomes in adults hospitalized with COVID-19 and hypoxemia, a phase III randomized trial showed.

Among 400 patients, the mean number of oxygen-free days was 13.4 for patients in the fostamatinib group and 14.2 for those in the placebo group (adjusted OR 0.82, 95% credible interval [CrI] 0.58-1.17), reported Sean P. Collins, MD, MSc, of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues.

Mortality was also higher at 28 days in the fostamatinib group: 11.3% of patients died compared with 8.1% in the placebo group (aOR 1.44, 95% CrI 0.72-2.90), they noted in JAMA Network Open.

Fostamatinib was approved in 2018 to treat adults with chronic immune thrombocytopenia (ITP) who had an insufficient response to a previous treatment. It blocks activation of neutrophils, macrophages, and platelets, each of which contribute to thromboinflammation in COVID-19.

In vitro data have demonstrated the ability of fostamatinib to inhibit the release of neutrophil extracellular traps in healthy neutrophils stimulated with COVID plasma. Through these mechanisms, fostamatinib is thought to mitigate acute lung injury caused by the virus.

A previous phase III randomized trial showed that fostamatinib plus standard care reduced the number of days on supplemental oxygen and improved clinical status in hospitalized COVID patients.

The current study is part of the NIH’s fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-4) program, which was created to quickly evaluate possible therapies targeting the host response for the treatment of COVID.

Earlier trials of fostamatinib had suggested that it might be effective in a population of unvaccinated COVID patients who had fewer comorbidities, Collins told MedPage Today.

“Our data suggest it does not work in the current population of patients with the more recent strains of COVID-19, who are highly vaccinated, older, and with a greater number of comorbidities,” he said. “However, given its mechanism of action, studying the utility of fostamatinib in other infectious conditions may be worthwhile.”

“Given the neutral outcome across our primary and key secondary outcomes, our data suggest another trial of fostamatinib in COVID-19 is not needed. It is unlikely that another primary outcome would have been positive,” he added.

Amesh Adalja, MD, of the Johns Hopkins Center for Health Security in Baltimore, noted that “fostamatinib is not being used widely (or probably at all) in the treatment of COVID-19 or any other respiratory infections.”

Another outcome that was evaluated in the study was being free of respiratory failure at day 28, defined as being alive and not receiving high-flow nasal oxygen, noninvasive ventilation, or invasive mechanical ventilation. “Other measures that would be meaningful could include hospital length of stay, duration of mechanical ventilation, and ICU length of stay,” Adalja told MedPage Today.

“It could be beneficial to see if specific subgroups of severe COVID might benefit. But benefit is harder and harder to show given the level of immunity in the population and the much-improved standard of care with severe COVID in the current era,” he said.

This double-blinded trial was conducted at 41 sites in the U.S. and 21 international sites from November 2021 through September 2023 among 400 adults who were positive for COVID and also had new-onset hypoxemia, defined as less than 92% oxygen saturation (SpO2) on room air, use of supplemental oxygen to maintain an SpO2 higher than 92%, or — for patients who had been receiving supplemental oxygen before their COVID diagnosis — an increased need for oxygen.

Median patient age was 67, 52.5% were men, 74.5% were white, and 11.8% were Black. Most patients (72.3%) had been vaccinated against COVID, and 35.8% had chronic pulmonary disease, with 11.5% using supplemental oxygen at home before they were hospitalized.

Of these patients, 199 received fostamatinib 150 mg orally twice daily for 14 days and 201 received placebo.

More patients had aspartate aminotransferase elevation in the fostamatinib group (11.6% vs 5.5% in the placebo group; aOR 2.28, 95% CrI 1.07-4.84). Other safety outcomes, including neutropenia and hypertension, were similar between groups.