New Arrows in our Quiver, to direct against SARS-CoV-2 variants

D. Suryaprabha*

Senior Executive – Clinical Research, Kauvery Hospitals, India

*Correspondence: Tel.: +91 98414 86267; email: suryaprabha@kauveryhospital.com

Abstract

Background: New treatments are needed, to be administered early in the evolution of the disease, to reduce the risk of progression of coronavirus disease 2019 (COVID-19).

Methods: A summary of new, upcoming, drugs in COVID-19 has been provided here.

Conclusion: New drugs are emerging with therapeutic benefits early in infection with SARS-CoV-2. These may be the new arrows in our quiver, to aim at early eradication of the virus and thereby prevent its progression to severe, critical, and fatal disease.

Keywords: Monoclonal Antibodies, COVID-19, Pilot, Pandemic, Omicron, FDA

Background

Coronavirus disease 2019 (COVID-19) is defined as an illness caused by a novel coronavirus, now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified at an outbreak of respiratory illness, causing pneumonia, at Wuhan City, Hubei Province, China [1]. It was initially reported to the WHO on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency. On March 11, 2020, the WHO declared COVID-19 a global pandemic, its first such designation since declaring H1N1 influenza a pandemic in 2009. New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (COVID-19). The number of confirmed COVID-19 cases worldwide has surpassed 400 million, including 5,770,023 deaths, reported to WHO according to the latest data.

Discussion

Sotrovimab

On May 27, 2021, emergency use authorization (EUA) was issued by the FDA for Sotrovimab, for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19). Eligible patients were adults, and paediatric patients aged ≥12 years who weigh ≥40 kg, with positive results on acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who were at high risk for progression to severe COVID-19, including hospitalization or death.

It is administered in the dose of 500 mg, as a single IV infusion, and administered as soon as possible after positive results of SARS-CoV-2 viral testing, and within 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization.

This includes patients who are older, immunocompromised, having underlying conditions like diabetes, hypertension, and obesity, and those unvaccinated [2]. Sotrovimab is an alternative to casirivimab-imdevimab, a monoclonal antibody cocktail recommended by WHO in September 2021. Studies are ongoing on the effectiveness of monoclonal antibodies against Omicron but early laboratory studies show that sotrovimab retains its activity [2].

Bebtelovimab

On February 11, 2022, FDA has authorized bebtelovimab for emergency use for certain non-hospitalized patients with mild-to-moderate COVID-19 at high risk of progression to severe disease for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. Bebtelovimab is being studied for the treatment of mild-to-moderate COVID-19 both as a monotherapy and together with other mAbs. Bebtelovimab (LY-CoV1404; LY3853113) is a neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2 that maintains binding and neutralizing activity across currently known and reported variants of concern, including Omicron and BA.2. Possible side effects of Bebtelovimab include anaphylaxis and infusion-related reactions, nausea, diarrhoea, dizziness, headache, itching, and vomiting [3]. It is administered in the dose of 175 mg, as a single IV injection over at least 30 sec. It is to be administered as soon as possible after positive results of SARS-CoV-2 viral testing and within 7 days of symptom onset.

Ritonavir – Boosted Nirmatrelvir (Paxlovid)

The U.S. FDA issued an emergency use authorization (EUA) for Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg or about 88 pounds) with positive results of SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

It consists of nirmatrelvir, which inhibits a SARS-CoV-2 protein to stop the virus from replicating, and ritonavir, which slows down nirmatrelvir’s breakdown to help it remain in the body for a longer period at higher concentrations. It is administered as three tablets (two tablets of nirmatrelvir and one tablet of ritonavir) taken together orally twice daily for five days, for a total of 30 tablets. It is not authorized for use for longer than five consecutive days. Possible side effects of Paxlovid include impaired sense of taste, diarrhoea, high blood pressure and muscle aches. Using Paxlovid at the same time as certain other drugs may result in potentially significant drug interactions. Using Paxlovid in people with uncontrolled or undiagnosed HIV-1 infection may lead to HIV-1 drug resistance. Ritonavir may cause liver damage, so caution should be exercised when giving Paxlovid to patients with preexisting liver diseases, liver enzyme abnormalities, or liver inflammation [3].

Evusheld (tixagevimab co-packaged with cilgavimab)

AstraZeneca’s Evusheld (tixagevimab co-packaged with cilgavimab), a long-acting antibody (LAAB) combination, has received emergency use authorisation (EUA) in the US for the pre-exposure prophylaxis (prevention) of COVID-19, with first doses expected to become available very soon. It is a combination of two long-acting monoclonal antibodies and is the only antibody therapy authorised in the US for COVID-19 pre-exposure prophylaxis and the only COVID-19 antibody delivered as an intramuscular dose (150 mg tixagevimab and 150 mg cilgavimab). It neutralises all previous SARs-CoV-2 variants to date. Studies are underway to provide information on the impact of the new Omicron variant (B.1.1.529) on Evusheld. It was formerly known as a combination of two LAABs – tixagevimab (AZD8895) and cilgavimab (AZD1061) – derived from B-cells donated by convalescent patients after SARS-CoV-2 virus [4,5].

Conclusion

Scientific community is actively searching for new solutions to address the challenges posed by SARSCoV2 infection. Studies are emerging on new drugs observed to have promising features in fighting SARS-CoV-2 virus. The first crop of antivirals against SARS-CoV-2 is promising. They are the new arrows in the quiver for directing against COVID-19 [6]. More drugs may be in the offing.

References

  1. CDC. 2019 Novel Coronavirus, Wuhan, China. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. 2020 Jan 26; Accessed: March 25, 2020.
  2. https://www.who.int/news/item/14-01-2022-who-recommends-two-new-drugs-to-treat-COVID-19
  3. https://www.fda.gov/news-events/press-announcements/coronavirus-COVID-19-update-fda-authorizes-monoclonal-antibody-treatment-COVID-19
  4. https://www.astrazeneca.com/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-authorised-for-emergency-use-in-the-us-for-pre-exposure-prophylaxis-prevention-of-COVID-19.html
  5. Dong J, et al. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail. bioRxiv. 2021; doi: 10.1101/2021.01.27.428529.
  6. https://www.nature.com/articles/d41586-022-00112-8
D.-Suryaprabha

D. Suryaprabha

Senior Executive-Clinical Research

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