Over the last century, advances in clinical immunology have led to the rise of immune globulin therapy in the treatment of infectious diseases [1]. From the 1918 influenza pandemic to more recent Ebola outbreaks, immune globulin has had varying success as a treatment method against these diseases [1]. Now, they are being considered as a potential treatment for COVID-19. Bamlanivimab and etesevimab are two such immunoglobulin antibodies [2]. Both bamlanivimab and etesevimab were issued emergency use authorization by the FDA for treating select patients experiencing mild to moderate cases of COVID-19, though that authorization for bamlanivimab administered alone was later revoked due to a lack of evidence supporting the benefit of that treatment [2].
There is good reason to suspect that bamlanivimab and etesevimab may be effective treatments for COVID-19 [2]. Both antibodies latch onto the overlapping epitopes in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, the protein central to the mechanism of COVID-19 infection [2, 3]. To use them for treatment purposes, researchers recovered etesevimab and bamlanivimab samples from the plasma of COVID-19 patients in China and the United States, respectively [4].
Since their isolation, bamlanivimab plus etesevimab has been tested in a few prominent clinical trials [2]. Perhaps the most prominent set of trials was BLAZE-1 [2]. In the second phase of BLAZE-1, researchers infused 612 COVID-19 patients with either 2,800 mg of bamlanivimab, 2,800 mg of bamlanivimab and 2,800 mg of etesevimab, or a placebo [2]. On day eleven, they reported significantly lower levels of viral load in the joint bamlanivimab-etesevimab group compared to placebo [2]. Notably, the group that received just bamlanivimab did not have considerably reduced viral loads compared to the placebo group [2].
Following these promising results, the BLAZE-1 group conducted a third phase trial [5]. That time, they analyzed 1,035 COVID-19 patients and distributed them into only two groups that would receive either bamlanivimab-etesevimab or a placebo [5]. While ten patients in the latter group died of COVID-19, no patients in the former did [5]. Additionally, hospitalization occurred at significantly reduced rates in the bamlanivimab-etesevimab compared to the placebo group [5]. Further trials, such as those conducted by Webb et al. and Rainwater-Lovett et al., have also reported reduced hospitalizations and emergency department visits among patients who received bamlanivimab plus etesevimab [6].
Despite these promising results, this treatment option carries some risks that may render it unsuitable for some patients. Nausea and diarrhea are among the most common adverse events (AE) associated with bamlanivimab plus etesevimab [3]. Other AEs include pruritus without rush and oral tingling [6]. Although these events might not be of the utmost severity, studies indicate that significantly more serious events–such as syncope, chest pain, and anaphylaxis–could also result from this treatment option [2, 6].
Furthermore, there is currently a lack of data concerning whether patients who are not hospitalized and/or do not require oxygen supplementation should receive bamlanivimab plus etesevimab [6]. For now, the FDA indicates that only patients who weigh 40 kg or more, are 12 or older, and are “at high risk of progressing to severe disease and/or hospitalization” should receive the treatment [2]. In addition, the emergency use authorization has been further restricted based on data that some SARS-CoV-2 variants display resistance to bamlanivimab plus etesevimab.
In the end, bamlanivimab plus etesevimab does seem like a promising treatment option for certain COVID-19 patients. Nevertheless, it requires more testing to determine what type of patients may profitably receive it and how sustainable it would be as a long-term treatment method [6].
References
[1] D. R. Kuritzkes, “Bamlanivimab for Prevention of COVID-19,” JAMA, vol. 326, no. 1, p. 31-32, June 2021. [Online]. Available: https://doi.org/10.1001/jama.2021.7515.
[2] The Medical Letter, “An EUA for Bamlanivimab and Etesevimab for COVID-19,” The Medical Letter, vol. 5, no. 63, p. 49-50, April 2021. [Online]. Available: https://secure.medicalletter.org/TML-article-1621a.
[3] P. Balasundaram and T. Morgan-Joseph, “Etesevimab,” StatPearls, Updated June 2021. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK572103/.
[4] Y. Shao, J. Chen, and H. Lu, “Update: Drug treatment options for coronavirus disease 2019 (COVID-19),” Bioscience Trends, p. 1-5, August 2021. [Online]. Available: https://doi.org/10.5582/bst.2021.01346.
[5] M. Dougan et al., “Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19,” The New England Journal of Medicine, July 2021. [Online]. Available: https://doi.org/10.1056/NEJMoa2102685.
[6] M. Tuccori et al., “An overview of the preclinical discovery and development of bamlanivimab for the treatment of novel coronavirus infection (COVID-19): reasons for limited clinical use and lessons for the future,” Expert Opinion on Drug Discovery, p. 1-12, July 2021. [Online]. Available: https://doi.org/10.1080/17460441.2021.1960819.
