By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: A retrospective study found that bebtelovimab has efficacy similar to that of nirmatrelvir/ritonavir (Paxlovid) in the treatment of high-risk outpatients with recent onset of COVID-19 who have mild to moderate symptoms.
SOURCE: Razonable RR, O’Horo JC, Hanson SN, et al. Outcomes of bebtelovimab treatment is comparable to ritonavir-boosted nirmatrelvir among high-risk patients with coronavirus disease-2019 during SARS-CoV-2 BA.2 Omicron epoch. J Infect Dis 2022; Sep 17:jiac346. doi: 10.1093/infdis/jiac346. [Online ahead of print].
Razonable and colleagues retrospectively examined the Mayo Clinic experience with the use of bebtelovimab and of nirmatrelvir/ritonavir (Paxlovid) in the treatment of high-risk adults with COVID-19 at a time when an Omicron variant of SARS-CoV-2 was prevalent. Patients meeting the requirements of the emergency use authorization regarding age and comorbidities and whose mild to moderate symptom onset was within five days for nirmatrelvir/ritonavir or seven days for bebtelovimab were included. The former was administered twice daily for five days while the monoclonal antibody was administered in a single 150-mg one-minute intravenous infusion.
Among the total cohort of 3,607 patients, the median age was 66.2 years and 94.9% were white. Only 16.2% were immunosuppressed. There was an imbalance between the two therapy cohorts, with the 774 bebtelovimab recipients being older and having a larger number of comorbidities, including immunocompromise (20.0% vs. 2.7%). The 2,833 nirmatrelvir/ritonavir recipients had a higher body mass index and greater proportion with diabetes mellitus. Approximately 93% in each group had completed a primary vaccination regimen.
Overall, 50 (1.4%) of 3,607 patients progressed to a severe outcome within 30 days of treatment, with no difference between the two treatment groups. Thus, this occurred in 1.4% (95% confidence interval [CI], 1.2% to 1.7%) of bebtelovimab recipients and 1.2% (95% CI, 0.8% to 1.5%) of those treated with nirmatrelvir/ritonavir. Intensive care was required by 0.5% and 0.3%. Six patients, all in the bebtelovimab group, died, with two of these deaths due to respiratory failure caused by COVID-19, while the other four were due to cancer or cardiac causes.
COMMENTARY
The U.S. Food and Drug Administration gave emergency use authorization of bebtelovimab in February 2022 for the outpatient treatment of high-risk patients with mild to moderate COVID-19 within seven days of symptom onset. In the absence of adequate clinical data, this approval was based on evidence of in vitro susceptibility of SARS-CoV-2 pseudovirus, including pseudovirus representing Omicron BA.2, to the monoclonal antibody.
Because of the limited clinical data, the National Institutes of Health has been recommending that bebtelovimab use be limited to “circumstances when use of both ritonavir-boosted nirmatrelvir (Paxlovid) and remdesivir are not available, feasible to use, or clinically appropriate.”1 This was graded as a weak recommendation based only on expert opinion. Another antiviral, molnupiravir, is less effective than these two agents. The need for three daily intravenous infusions of remdesivir makes its use problematic for some patients as well as for some therapy centers. The multiple drug interactions of the ritonavir component of Paxlovid make it difficult or impossible to use in many patients — a likely explanation of the greater prevalence of morbidities, including immunosuppression, in the patients for whom bebtelovimab was chosen because of the need to use interacting medications in their ongoing management.
The virus has evolved with progressive escape from inhibition by anti-spike monoclonal antibodies. Thus, bebtelovimab replaced sotrovimab, which previously had replaced bamlanivimab/etesevimab for the outpatient treatment of mild to moderate COVID-19 because of the development of viral resistance. Current evidence indicates that bebtelovimab retains in vitro activity against many currently circulating and emerging Omicron subvariants, including, e.g., BA.4.6 and BA.2.75.
Although this retrospective study is not randomized, the results are valuable and indicate that bebtelovimab has clinical efficacy similar to that of nirmatrelvir/ritonavir. While the latter has the advantage over both bebtelovimab and remdesivir of being an orally administered agent, the multiple drug interactions must be considered carefully when prescribing it. In many patients, bebtelovimab may be the preferred agent.
REFERENCE
- National Institutes of Health. COVID-19 Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov
