Therapeutic agents treat patients who test positive for COVID-19

Vaccines are still the best preventive strategy for COVID-19, but there is still a need for treatments that help prevent the progression to serious illness, especially for high-risk patients.

Monoclonal antibody

Monoclonal antibodies (mAbs) have the potential to prevent and treat COVID-19 by binding to the epitope of the SARS-CoV-2 pedromer protein and neutralizing the virus. Such treatments that directly target SARS-CoV-2 are expected to be most effective early in the course of the disease if the etiology is primarily caused by viral replication. Therefore, people with a positive test result should start treatment as soon as possible. The three anti-SARS-CoV-2mAbs have received an Emergency Use Authorization (EUA) for mild to moderate COVID-19 for people at high risk of progression (see table).¹). Tixagevimab and cilgavimab (Evusheld) are the fourth EUA-based anti-SARS-CoV-2mAb of COVID-19. However, it is only approved for pre-exposure prophylaxis in immunocompromised patients who may not respond adequately to vaccination or who have a history of serious side effects to available vaccines.² Its efficacy against Omicron variants has been determined.

Bamlanivimab and ethesebimab are neutralized mAbs that bind to different but overlapping epitopes of peplomer.³ A Phase 3 study of 1035 patients showed a 4.8% reduction in absolute risk (ARR) in death or hospitalization of patients receiving combination therapy compared to placebo.^Four These are the only mAbs available to young pediatric patients, including newborns, primarily based on pharmacokinetic studies. However, efficacy may vary depending on the major circulating strain.³

Casilibimab and imdebimab are recombinant mAbs that bind to non-overlapping epitopes of peplomer proteins. A single intravenous infusion, also known as the cocktail REGEN-CoV, was associated with 2.2% ARR at death or hospitalization compared to placebo.^1,5 REGEN-COV, a combination of mAb casilivimab and imdevimab, reduced viral load and the number of visits in COVID 2019 patients (COVID-19 REGEN-CoV is also available as a subcutaneous injection and tends to increase access. Management to external clinic and hospital settings, but requires 1 hour of monitoring).

Sotrovimab is a pan-salvecovirus mAb that showed an ARR of 4.5% on death or hospitalization compared to placebo.⁶ Sotrovimab is expected to pose a high barrier to resistance as it can target epitopes outside of rapidly evolving motifs and retain activity against new mutants of concern.⁷ In a study assessing the invitro neutralizing activity of anti-SARS-CoV-2mAb, sotrovimab was the only drug approved for treatment that retained activity against the Omicron variant.⁸

Emerging agent

Although mAbs represent a milestone in COVID-19 management, new oral antivirals such as Mornupiravir nilmatrelvir and ritonavir (Paxlovid) are of disease due to accessibility, management, and monitoring requirements. A welcome intervention to prevent progression.

Molnupiravir is a prodrug that introduces transcriptional errors into viral RNA and impairs SARS-CoV-2 replication. Results from a phase 3 study in 1433 patients showed 3% ARR for molnupiravir mortality and hospitalization (95% CI, –5.9–0.1) compared to placebo.⁹ Paxlovid is a protease inhibitor that also targets viral replication. Results from a Phase 2/3 study of 2246 patients showed a 0.8% mortality or hospitalization rate for Paxlovid compared to 6.3% for placebo when administered within 5 days of onset of symptoms.^Ten Paxlovid contains ritonavir, which slows the metabolism of nirmatorelvir through cytochrome P450 inhibition. However, it also makes it prone to drug interactions that require pharmacists to be very vigilant when dispensing. Both drugs have been issued an EUA that begins as soon as possible after diagnosis and within 5 days of the onset of symptoms to prevent the progression of high-risk patients with mild to moderate COVID-19.^10,11 Paxlovid is approved for patients over 12 years of age who weigh 40 kg or more. However, molnupiravir is not recommended for children and pregnant women due to the potential risk of embryonic fetal toxicity and impaired bone and cartilage growth seen in nonclinical studies. No data are available to support the use of Paxlovid during pregnancy.^10,11

Diversion of existing drugs is another approach to identifying potential drugs for COVID-19. Fluvoxamine is the first of many reused drugs that have shown mortality benefits.¹² As an oral selective serotonin reuptake inhibitor and alpha 1 receptor (S1R) agonist, the potential mechanism for COVID-19 is through the regulation of S1R in cytokine production in response to inflammatory triggers. The results of an adaptive platform trial in 1497 patients showed 5% ARR hospitalization with fluvoxamine compared to placebo.¹²

Conclusion

Treatment management for COVID-19 has evolved by understanding the clinical course of infection. As studies continue to emphasize the importance of early intervention in mild to moderate disease, pharmacists keep information on therapies used to control, prevent, and treat COVID-19 infections up to date. is needed.

Sara Lee, PharmD, Is a PGY2 infectious disease pharmacy resident at the New York Presbyterian Hospital in New York, NY.

References

1. Taylor PC, Adams AC, Hufford MM, de la Torre I, Winthrop K, Gottlieb RL. Neutralizing monoclonal antibody for the treatment of COVID-19. Nat Rev Immunol.. 2021; 21 (6): 382-393. doi: 10.1038 / s41577-021-00542-x

2. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institute of Health. Updated December 16, 2021. Accessed December 19, 2021. https://www.covid19treatmentguidelines.nih.gov

3. Dougan M, Nirula A, Azizad M, et al .; BLAZE-1 Researcher. Bamlanivimab and etesebimab in mild or moderate COVID-19. N Engl J Med.. 2021; 385 (15): 1382-1392. doi: 10.1056 / NEJMoa2102685

4. REGEN-CoV (casirivimab and imdevimab) Healthcare Provider Emergency Use Authorization (EUA) fact sheet. FDA. Updated in November 2021. Accessed on December 19, 2021. https: //www.fda.gov/media/145611/download

5. Gupta A, Gonzalez-Rojas Y, Juarez E, et al .; COMET-ICE Researcher. Early treatment of COVID-19 with the SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med.. 2021; 385 (21): 1941-1950 doi: 10.1056 / NEJMoa2107934

6. Kabinger F, Stiller C, Schmitzová J, etc. Molnupiravir-induced SARS-CoV-2 mutagenesis mechanism. Nat Struct Mol Biol.. 2021; 28 (9): 740-746 Doi: 10.1038 / s41594-021-00651-0

7. Molnupiravir, an oral antiviral drug in the Merck and Ridgeback trial, has an approximately 50 risk of hospitalization or death compared to placebo in patients with mild or moderate COVID-19 in a positive interim analysis of Phase 3 trials. % Reduced. Merck. news release. October 1, 2021. Accessed on November 6, 2021. https: //www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-Compare with placebo in mild or moderate patients And about 50% /

8. Molnupiravir, an oral COVID-19 antiviral drug from Merck and Ridgeback, is the first in the world to be licensed. Merck. news release. November 4, 2021. Accessed on December 19, 2021. https: //www.merck.com/news/merck-and-ridgebacks-molnupiravir-an-oral-covid-19-antiviral-medicine-receives-first-authorization-in -world /

9. Reis G, dos Santos Moreira-Silva EA, Silva DCM, etc. Effect of early treatment with fluvoxamine on emergency care and hospitalization risk for COVID-19 patients: a jointly randomized platform clinical trial. Lancet Globe Health.. 2022; 10 (1): e42-e51 doi: 10.1016 / S2214-109X (21) 00448-4

10. Hirshberg JS, Cooke E, Oakes MC, Odibo AO, Raghuraman N, Kelly JC. Monoclonal antibody therapy for symptomatic COVID-19 during pregnancy: initial report. This is JObstet Gynecol.. 2021; 225 (6): 688-689. doi: 10.1016 / j.ajog.2021.08.025