CCM investigators: monoclonal antibody trial results
UPMC and Pitt Provide First Results of Largest Comparative Randomized Trial of Monoclonal Antibody Treatment for COVID-19
PITTSBURGH (9/8/2021) – Monoclonal antibodies—an outpatient treatment that must be given soon after COVID-19 diagnosis—significantly decrease hospitalization and death from the disease. Real-world data from UPMC patients now show that two antibody combination treatments—bamlanivimab-etesevimab and casirivimab-imdevimab—were safe and appeared to be equally effective.
These interim results come from UPMC’s innovative OPTIMISE-C19 study, a randomized, adaptive trial designed to simultaneously expand access to monoclonal antibodies and compare the effectiveness of different treatments for outpatients with COVID-19. The next phase of the trial, which already is in progress, will evaluate how well the currently authorized treatments work against coronavirus variants, including Delta, to prevent hospitalization and death.
“Before we launched OPTIMISE-C19, only a small percentage of eligible patients were receiving monoclonal antibody treatment,” said lead author Erin McCreary, Pharm.D., UPMC infectious diseases pharmacist and Pitt clinical assistant professor of medicine. “Now, we’re able to offer monoclonal antibodies in the context of a clinical trial at every single one of our available treatment sites—resulting in a 7.5-fold increase in the number of eligible patients receiving this treatment. That level of outreach and access is virtually unprecedented, allowing us to build a foundation to roll-out future treatments quickly and safely within our learning health system.”
Monoclonal antibodies are potent versions of the natural defense that our bodies build to fight off an infection. By giving monoclonal antibodies to newly infected people, they can immediately start neutralizing and eliminating the virus, preventing it from infecting cells and causing damage. Previous research by UPMC and others found that monoclonal antibodies significantly reduce the risk of hospitalization and death when given soon after infection.
“The whole world is in a race to tame the virus that causes COVID-19,” said study co-author Derek Angus, M.D., M.P.H., UPMC’s chief innovation officer and distinguished professor and chair of Pitt’s Department of Critical Care Medicine. “If we get COVID-19, monoclonal antibodies are currently our best bet to keep ourselves and our loved ones alive and out of the hospital. In our quest for a cure, we’ve had the good fortune to have multiple options available, leaving doctors with the question: Which one is best for my patient? Right now, the answer is that the best option is the one you can give your patient fastest.”
In February 2021, UPMC partnered with the White House COVID-19 Response Team to expand clinical use of monoclonal antibodies and evaluate their comparative effectiveness.
The OPTIMISE-C19 trial randomizes the allocation of the monoclonal antibody treatments that were granted emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA) to patients who qualify for them. All patients in the trial receive monoclonal antibody treatment, are followed for 28 days and their outcomes compared.
UPMC randomized either Eli Lilly or Regeneron’s combination monoclonal antibody treatment to 1,935 patients from March 10 to June 25, 2021. The results were pulled for analysis after the federal government stopped distributing Lilly’s monoclonal antibody treatment due to lower laboratory effectiveness against the Gamma and Beta variants of the virus.
The first results of OPTIMISE-C19 show that before Delta became the predominant strain in the U.S., both Lilly and Regeneron’s combination monoclonal antibody treatments performed well in keeping patients with COVID-19 alive and out of the hospital in a geographic region of Alpha variant predominance. Safety also was similar, with very few serious complications due to the treatment among UPMC patients.
While data were pulled for analysis, GSK and Vir Biotechnology’s monoclonal antibody, sotrovimab, was granted an EUA and incorporated into UPMC’s OPTIMISE-C19 trial for comparison against Regeneron’s treatment.
“That’s the beauty of an adaptive learning health system trial,” said senior author and principal investigator David Huang, M.D., M.P.H., an intensivist at UPMC and professor of critical care medicine, emergency medicine, and clinical and translational science at Pitt. “As new treatments are authorized, we can immediately begin offering them to patients and collect randomized data to inform future treatment protocols. We can then compare outcomes as the virus evolves and new variants emerge.”
Delta is now the predominant strain of COVID-19 in the communities UPMC serves. UPMC offers monoclonal antibodies to people who have tested positive for COVID-19, have had symptoms for 10 days or less and meet other FDA eligibility criteria. Certain people who have been exposed to COVID-19 also can receive monoclonal antibodies as a preventive treatment, to keep them from contracting the virus. More information can be found at www.upmc.com/antibodytreatment or by calling 866-804-5251.
Additional authors on this research are J. Ryan Bariola, M.D., Tami Minnier, M.S., Richard J. Wadas, M.D., Judith A. Shovel, B.S.N., Debbie Albin, B.S., Oscar C. Marroquin, M.D., Kevin E. Kip, Ph.D., Kevin Collins, M.B.A., Mark Schmidhofer, M.D., Mary Kay Wisniewski, M.A., David A. Nace, M.D., Colleen Sullivan, M.H.A., Meredith Axe, B.S., Russell Meyer, M.B.A., Alexandra Weissman, M.D., William Garrard, Ph.D., Stephen Koscumb, B.S., Octavia M. Peck-Palmer, Ph.D., Alan Wells, M.D., Robert D. Bart, M.D., Anne Yang, M.D., Tina Khadem, Pharm.D., Kelsey Linstrum, M.S., Stephanie K. Montgomery, M.S., Daniel Ricketts, M.T., Jason Kennedy, M.S., Caroline J. Pidro, B.S., Ghady Haidar, M.D., Graham M. Snyder, M.D., Bryan J. McVerry, M.D., Christopher W. Seymour, M.D., and Paula L. Kip, Ph.D., all of UPMC, Pitt or both; and Lindsay Berry, Ph.D., Scott Berry, Ph.D., Amy Crawford, Ph.D., and Anna McGlothin, Ph.D., all of Berry Consultants. Donald M. Yealy, M.D., UPMC’s chief medical officer and professor and chair of Pitt’s Department of Emergency Medicine, provided data and safety monitoring for the trial.
The U.S. government provided the monoclonal antibody treatments reported in this manuscript.