SAN FRANCISCO, March 12, 2021 /PRNewswire/ -- 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.
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), commented, "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."
"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," continued 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.
"While Amgen is also disappointed that apremilast did not meet the predefined, high treatment effect required in this trial for patients hospitalized with COVID-19 who are in the ICU or have a high oxygen need, as compared to the control, we appreciate the ability of the I-SPY COVID Trial investigators to generate meaningful data rapidly," said Elliott Levy, senior vice president of R&D strategy and operations, Amgen. "We all worked as a team to quickly execute the study and would like to take this opportunity to thank the study participants."
"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."
Quantum Leap Healthcare Collaborative is a 501C(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our mission is to integrate high-impact research with clinical processes and systems technology, resulting in improved data management and information systems, greater access to clinical trial matching and sponsorship, and greater benefit to providers, patients and researchers. Our goal is to improve and save lives. Quantum Leap provides operational, financial, and regulatory oversight to the I-SPY Trials. For more information, visit www.QuantumLeapHealth.org.
The I-SPY Trials were designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 20 major U.S. medical research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations. For more information, visit www.ispytrials.org.
SOURCE Quantum Leap Healthcare Collaborative