The nation has been coping with the pandemic for more than a year, and in this time, researchers have learned a great deal about how to treat COVID-19. Yet they have also been faced with what they still must learn, including how to reach the individuals who have been most dramatically impacted by the disease and who could benefit the most from new treatments.
A new $8.7 million grant from the National Institutes of Health (NIH) will fuel these efforts for the next two years. Adit Ginde, MD, MPH, professor of emergency medicine at CU School of Medicine and UCHealth emergency physician is leading a team of researchers from the Colorado Clinical and Translational Sciences Institute at the University of Colorado Anschutz Medical Campus to test the real-world effectiveness of a promising treatment for high-risk COVID-19 outpatients. At the same time, they will study the best way to reach the population at the greatest risk of serious disease and hospitalization, focusing on racial/ethnic minorities, older adults and those with underlying conditions.
The treatment Dr. Ginde and his team will be testing is neutralizing monoclonal antibodies (MAbs) directed against the SARS-CoV-2 virus, which is perhaps the most promising antiviral agent used in an outpatient setting.
“Monoclonal antibodies reduced the risk of hospitalizations in high-risk outpatients by 85-87% in two recent phase three clinical trials,” Ginde says. And though clinicians would like to see the published data before they can say there is definitive proof, there is enough evidence of clinical benefit that in November 2020, the FDA gave emergency use authorization to use MAbs in high-risk outpatients for this purpose.
Once the FDA authorized use of MAbs (made by Eli Lilly and Regeneron), public health authorities and health systems across the state expected to see huge demand for the treatment. “If every eligible patient [in Colorado] would have received the treatment, we would have run out of the medicine in two to three days,” says Ginde.
The fact is that less than 5% of those who qualify for treatment actually receive it. Further, most patients accessing MAb treatment to date are white and non-Hispanic, which does not reflect the disproportionately high need to deliver effective treatments to racial and ethnic minority communities at higher risk of severe disease. “The U.S. government has spent literally billions of dollars on developing effective therapeutics, but it is mostly for naught if we can’t effectively deliver these therapies to patients who need them,” Ginde says.
Ginde says the medical and public health communities are looking for scalable solutions for rapid and equitable use of MAbs in high-risk outpatients, while simultaneously providing real-world confirmatory evidence of their effectiveness.
Part of the low uptake of the MAb treatment has to do with the provider-patient relationship in the era of COVID-19 playing out in a very different paradigm. Because of the way COVID-19 testing is happening, primary care physicians may not even know that their patients are positive. Even if providers do know a patient is positive, they may not know about this treatment. This is further complicated by the fact that MAbs are given through an intravenous infusion. It takes about one hour to infuse the medicine and then patients are observed for an hour afterwards. There are 30 infusion sites across Colorado, including four sites at UCHealth.
The project will leverage a highly experienced team of investigators to design and lead the effort, including implementation scientist Bethany Kwan, PhD, bioethicist Matthew Wynia, MD, biomedical informaticist Tell Bennett, MD and biostatistician Nichole Carlson, PhD.
The goal of the project is to reach at least 4,000 individuals, some who will receive the MAb treatment and some who will not. For three months, the study will follow the outpatients with telephone surveys and electronic health records to determine the effectiveness of the treatment in preventing hospitalization, emergency room visits and to track long-term symptoms. Ultimately, the project will provide real-world evidence on MAb treatments and inform the best practices for rapid dissemination of current and future outpatient COVID-19 therapies.
“We want to understand how to provide patients with access to this treatment, and to do so equitably. We need to reach the population of Coloradans that is more at risk to get the disease and more at risk to be hospitalized,” Ginde says.
This research project is supported by NIH grant number 3UL1TR002535-03S3.