Q&A: Monoclonal antibody combinations appear equally effective against COVID-19
In the largest comparative randomized trial of monoclonal antibody treatments for COVID-19, two regimens — bamlanivimab/etesevimab and casirivimab/imdevimab — were safe and appeared to be equally effective, according to a press release.
In the OPTIMISE-C19 trial, researchers from the University of Pittsburgh Medical Center compared the effectiveness of the combination regimens, both of which were authorized by the FDA for patients with mild to moderate COVID-19.
“Before we launched OPTIMISE-C19, only a small percentage of eligible patients were receiving monoclonal antibody treatment,” Erin McCreary, PharmD, an infectious disease pharmacist and clinical assistant professor of medicine at the University of Pittsburgh School of Medicine, said in the release. “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.”
McCreary and colleagues randomly assigned 1,935 patients with mild to moderate COVID-19 to receive bamlanivimab (Eli Lilly & Co.) alone, bamlanivimab/etesevimab (Eli Lilly & Co.) or casirivimab/imdevimab (REGEN-COV, Regeneron). The treatments were administered within 10 days of symptom onset. Patients were then followed for 28 days.
Between March 10 and June 25, McCreary and colleagues assigned 128 patients to receive bamlanivimab, 885 patients to receive bamlanivimab/etesevimab and 922 patients to receive casirivimab/imdevimab. The mean age of patients ranged from 55 to 57 years; about half were women; and 17% were Black.
When compared with bamlanivimab/etesevimab and casirivimab/imdevimab, bamlanivimab alone yielded a 91% and 94% probability of inferiority, respectively. The two combination therapies yielded an 86% probability of equivalence in efficacy, according to the researchers.
As Healio Primary Care previously reported, the combination treatment of bamlanivimab/etesevimab received an emergency use authorization (EUA) from the FDA in February. Casirivimab/imdevimab received an EUA in November 2020.
The EUA for bamlanivimab/etesevimab was based on data from a placebo-controlled trial that showed one IV infusion of the combination treatment significantly decreased COVID-19-related hospitalization and death at 29 days in patients with COVID-19 who were at high risk for disease progression.
The EUA for casirivimab/imdevimab was based on results from a randomized, double-blind, placebo-controlled trial. The study found that only 3% of patients receiving the treatment became hospitalized or visited the ED compared with 6% of patients receiving placebo.
Both combination treatments were authorized for patients aged 12 years or older weighing at least 88 pounds who tested positive for SARS-CoV-2.
“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,” David T. Huang, MD, MPH, a professor of critical care medicine, emergency medicine and translational science at the University of Pittsburgh School of Medicine, said in the release.
Healio Primary Care spoke with Huang to learn more about the monoclonal antibody treatments.
Healio Primary Care: What is the take-home message of your study for physicians?
Huang: Monoclonal antibodies are effective treatments to keep patients with COVID-19 out of the hospital. As to which is best, right now the answer is the one you can most quickly give your patient.
Healio Primary Care: Who are the ideal candidates for this treatment?
Huang: As per the FDA EUAs, the ideal candidates are patients with mild to moderate COVID-19, shortly after symptom onset, at high risk for deterioration (eg patients with comorbidities, older age, higher BMI).
Healio Primary Care: Does the efficacy of the treatment depend on which variant a patient is infected with?
Huang: Our trial did not directly measure variants at the patient level but found no difference in comparative effectiveness over time. However, the alpha variant was dominant throughout the trial period of March through June, with delta only becoming prevalent at the end, so this question is still an open one.
Healio Primary Care: What are the adverse events associated with this treatment that physicians should be aware of?
Huang: As per the EUAs, there are rare events such as allergic reactions. In our trial of 1,935 patients, 21 patients (1%) had an adverse event, of which only 5 (0.26%) were deemed serious.
Healio Primary Care: When do you predict the treatments will receive FDA approval?
Huang: That is hard to predict. The FDA’s focus right now is vaccine approvals.
Healio Primary Care: How do you approach patients who might really need this treatment but are skeptical or wary of it?
Huang: I would advise patients that monoclonal antibodies are safe and effective and can keep them out of the hospital and alive.
Healio Primary Care: Anything else to add?
Huang: The OPTIMISE-C19 trial, as a learning health system trial, continues to evaluate all available monoclonal antibodies, and we hope to provide additional comparative effectiveness data in the face of delta soon.
References:
FDA. COVID-19 Update: FDA authorizes monoclonal antibodies for treatment of COVID-19. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-monoclonal-antibodies-treatment-covid-19-0. February 10, 2021.
McCreary EK, et al. medRxiv. 2021;doi:10.1101/2021.09.03.21262551.
McGinley L and Johnson CY. Experimental drug given to Trump to treat covid-19 wins FDA clearance. https://www.washingtonpost.com/health/2020/11/21/regeneron-fda-clearance/. Accessed November 23, 2020.
UPMC. UPMC and Pitt provide first results of largest comparative randomized trial of monoclonal antibody treatment for COVID-19. https://www.upmc.com/media/news/090821-optimise-interim. Accessed September 13, 2021.