QLHC Concludes Apremilast Not Likely to Reduce Time to COVID Recovery, Mortality

Quantum Leap Healthcare Collaborative (QLHC), the sponsor of the I-SPY COVID Trial, announced that apremilast (Otezla), made by Amgen, has been dropped for futility. Apremilast was chosen for testing in the I-SPY COVID Trial because it is a phosphodiesterase-4 (PDE4) inhibitor hypothesized to blunt the cytokine storm that accompanies critical illness associated with COVID-19.

The I-SPY COVID Trial is a phase II, open label, adaptive platform trial being conducted in critically ill COVID-19 patients who are receiving high flow oxygen or mechanical ventilation. The trial was designed to rapidly screen agents to find those with the best chance of reducing time to recovery (defined as reduction in oxygen demand) by approximately 50% and reducing risk of death. The I-SPY COVID Trial identified the initial agents for the study through a unique partnership with the COVID R&D Alliance, and apremilast was the first agent identified and approved to go forward through this mechanism.

QLHC discontinued testing of apremilast (Otezla) in the I-SPY COVID Trial because, after 67 patients enrolled, the agent met the predefined futility criterion, defined as at least 90% probability that the hazard ratio for time to recovery is less than 1.5 compared to the control arm. The data from apremilast patients were compared to those from 133 patients concurrently randomized to the control, which included backbone therapy (consisting of dexamethasone and remdesivir). Patients assigned to the apremilast arm received backbone therapy in combination with 30 mg twice daily of apremilast for up to 14 days. Based on a near final analysis, there is a low probability that the addition of apremilast to backbone therapy reduces time to recovery, and there is no indication that it reduces mortality. As a result, the Data Monitoring Committee recommended closing the arm.

"The I-SPY COVID Trial suggests that adding apremilast to backbone therapy did not impact recovery in patients critically ill with COVID-19 when compared to those receiving backbone therapy alone," Dr. Karl Thomas, an I-SPY COVID Trial co-investigator and chaperone (PI) of the apremilast arm, and an associate professor of medicine at Wake Forest University (Winston Salem, North Carolina), said.

"While we were disappointed that apremilast did not succeed in altering the clinical course of critically ill COVID-19 ARDS patients when added to dexamethasone and/or remdesivir, we were glad to know this quickly and to move on to other agents that might be more effective for this particular group of patients," said Dr. Paul Berger, a professor of medicine at Sanford Health in South Dakota and co-principal investigator for the apremilast arm of the I-SPY COVID Trial.

"The investigators and the many individuals involved in this study are truly grateful to Amgen for proactively engaging with the I-SPY COVID Trial," said Laura Esserman, founder and co-principal investigator of the I-SPY Trials and director of the Carol Franc Buck Breast Care Center at UCSF. "By contributing a successful commercial drug to the trial for rigorous evaluation in the critical care setting, Amgen demonstrated the industry commitment to partnering and leveraging an adaptive platform study design to accelerate research and help combat the global pandemic."