Roche India and Cipla have announced the availability of the first batch of the antibody cocktail (casirivimab and imdevimab) in India for the treatment of mild to moderate COVID-19 in patients who are at high risk. With the increasing importance of the cocktail drug, this article portrays the working of monoclonal antibodies and the considerations and complications around it.

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What we need to know

In India, the Central Drugs Standards Control Organisation (CDSCO) has granted an Emergency Use Authorisation (EUA) for Roche's antibody cocktail for the treatment of coronavirus disease (COVID-19). India is the second nation to authorise Roche's COVID-19 antibody-drug cocktail casirivimab and imdevimab. CDSCO of India has expedited the authorisation of Roche's antibody-drug cocktail based on data submitted to the US FDA and the expert consensus of an European regulatory panel. The drug has been shown to decrease hospital stays in COVID-19 patients who are at a high likelihood of developing severe COVID-19.

Around 10 days after the onset of COVID-19, several people develop neutralising antibodies to SARS-CoV-2, with greater antibody levels in those with serious disease. The intensity of antibody responses to SARS-CoV-2 S and N proteins was associated with the neutralising behaviour of COVID-19 patients' plasma. In patients with mild to moderate COVID-19, monoclonal antibodies attacking the S protein have the capacity to avoid SARS-CoV-2 infection, mitigate symptoms, and restrict progression to serious disease, especially in those who still haven't evolved an endogenous antibody response.

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Anti-SARS-CoV-2 monoclonal antibodies approved for emergency use by the FDA

Bamlanivimab is a monoclonal antibody that is capable of neutralising the S protein of SARS-CoV-2. Etesevimab is a neutralising monoclonal antibody that binds to a separate yet overlapping epitope in the SARS-CoV-2 S protein's RBD. Casirivimab (previously REGN10933) and imdevimab (previously REGN10987) are human monoclonal antibodies that attach to non-overlapping epitopes of SARS-S CoV-2's protein RBD.

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Recommendations

Two combination drugs, bamlanivimab plus etesevimab and casirivimab plus imdevimab, are approved by the FDA for the management of mild to moderate COVID-19 in non-hospitalised patients with laboratory-confirmed SARS-CoV-2 infection who are at high risk of progressing to serious disease and/or hospitalisation.

• Bamlanivimab 700 mg plus etesevimab 1,400 mg
• Casirivimab 1,200 mg plus imdevimab 1,200 mg

According to IDSA recommendations, bamlanivimab/etesivimab can be used in patients with mild to moderate COVID-19 who are at high risk of developing severe illnesses. According to the FDA EUA, high-risk patients must meet at least one of the following requirements:

• Have a BMI of >35
• Have chronic kidney disorder
• Have diabetes
• Have immunosuppressive disease
• Are undergoing immunosuppressive treatment
• Are >65 years old
• Are 55 years old AND have cardiovascular disease, OR hypertension, OR chronic obstructive pulmonary disease/other chronic respiratory condition
• IDSA advises against bamlanivimab monotherapy in hospitalised patients with serious COVID-19
• Treatment should begin as soon as possible after a positive SARS-CoV-2 antigen or nucleic acid amplification test (NAAT) and within 10 days of the onset of symptoms.

Except in a clinical trial, the panel advises against using anti-SARS-CoV-2 monoclonal antibodies for COVID-19-infected patients who are hospitalised. Persons with mild to moderate COVID-19 that are hospitalised for a cause other than COVID-19 but following the EUA requirements should be considered for their use.

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Monoclonal antibodies against SARS-CoV-2 in patients hospitalised with COVID-19

The FDA EUAs do not allow the use of anti-SARS-CoV-2 monoclonal antibodies in patients hospitalised with COVID-19 or in the following patients:

1. Those who need oxygen therapy as a result of COVID-19; or
2. Those who are on ongoing oxygen therapy due to underlying non-COVID-19-related comorbid conditions and need an improvement in oxygen flow rate from baseline as a result of COVID-19.

The FDA's EUAs does allow for the use of these monoclonal antibodies in patients who are admitted for a reason other than COVID-19 who are at high risk of leading to serious disease and/or hospitalisation. Monoclonal antibodies to SARS-CoV-2 can be made available by extended access services for the care of immunocompromised patients hospitalised with COVID-19. It is unknown if these antibodies help individuals with B-cell immunodeficiency or other immunodeficiencies clinically. Monoclonal antibodies to SARS-CoV-2 have not been demonstrated to be effective in hospitalised patients with severe COVID-19.

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Observation

These anti-SARS-CoV-2 monoclonal antibodies should be delivered intravenously and should only be provided by eligible health care professionals who have direct access to drugs to control acute infusion reactions and emergency medical services. Patients should be observed during the infusion and for at least one hour afterwards. There is no need to change the dose for body weight, renal dysfunction, or moderate hepatic impairment.

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Complications

Nausea, diarrhoea, dizziness, fever, pruritis, and vomiting were the most often reported adverse events with bamlanivimab. Bamlanivimab's safety profile was stated to be comparable to that of the placebo.

The following adverse effects were recorded in the EUA fact sheet for bamlanivimab plus etesevimab:

• Nausea
• Dizziness
• Rash
• Pruritis
• Pyrexia

1% of participants in Phase 3 BLAZE-1 trial experienced hypersensitivity reactions, including infusion-related reactions, rash, and pruritis. Hypersensitivity reactions, such as anaphylaxis and infusion reactions, are possible.

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Drug-drug interactions

It is unlikely that bamlanivimab plus etesevimab or casirivimab plus imdevimab will interfere with drugs that are excreted by the kidneys or that are cytochrome P450 substrates, antagonists, or inducers.

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Vaccination

Vaccination against SARS-CoV-2 can be postponed for 90 days in individuals that have received anti-SARS-CoV-2 monoclonal antibodies. This is a precautionary measure, as antibody therapy can impair the immune responses caused by vaccines.

For individuals who acquire COVID-19 after SARS-CoV-2 vaccination, previous vaccination may have little impact on treatment choices, including the use and scheduling of monoclonal antibody treatment.

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Pregnancy considerations

As monoclonal immunoglobulin (Ig) G antibodies, bamlanivimab in combination with etesevimab, casirivimab in combination with imdevimab, and bamlanivimab alone can cross the placenta. There is no available evidence on the use of these anti-SARS-CoV-2 monoclonal antibodies during breastfeeding; however, IgG drugs are normally not withheld from use during pregnancy.

Anti-SARS-CoV-2 monoclonal antibodies should not be removed from pregnant women with COVID-19 who have a diagnosis that increases the likelihood of progression to extreme COVID-19 and the patient and physician agree that the possible value of the treatment outweighs the potential risk.

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Considerations in children

There is insufficient paediatric data to recommend anti-SARS-CoV-2 monoclonal antibody products for children with COVID-19 who are not hospitalised but have risk factors for severe disease.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.