Monoclonal antibody

What’s the evidence that REGEN-COV (casirivimab and imdevimab) monoclonal antibody cocktail is effective in the post-exposure prophylaxis of Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

The U.S. FDA has issued an Emergency Use Authorization (EUA) for the emergency use of REGEN-COV in adult and pediatric populations (≥12 years of age and older weighing> 40 kg) who are at high risk* of progression to severe COVID-19— including hospitalization or death— and who are not fully vaccinated or are not expected to mount an adequate immune response to the vaccine (eg, immunocompromised state).1  This recommendation is based on a randomized controlled trial involving individuals enrolled within 96 hours of exposure to a known Covid-19 case (Covid-10 Phase 3 Prevention Trial).2

In this trial, the primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28  in participants who did not have SARS-CoV-2 infection  by PCR or serology at the time of enrollment. Symptomatic SARS-CoV-2 infection developed in 1.5% of treatment group (vs 7.8% in placebo group) with 81.4% relative risk reduction (P<0.001); 66% reduction was observed when symptomatic and asymptomatic infections were combined.  Duration of symptoms and the magnitude and duration of detectable RNA were also lower in the REGEN-COV group compared to placebo. Therapy was well tolerated.2

In the same study, in a subgroup analysis of those who were seropositive at the time of enrollment REGEN-COV lowered the risk of symptomatic disease (0.4% vs 2.3% in the placebo group) with relative risk reduction of 81%, though not statistically significant (P=0.14).  This may be why the FDA EUA extended to certain vaccinated groups as well since to date there are no published trials on the use of REGEN-COV as post-exposure prophylaxis in vaccinated individuals.

*High risk group included ≥65 years of age, BMI≥25 kg/m2, diabetes, immunocompromised state, cardiovascular disease or hypertension, chronic lung disease, sickle cell disease and neurodevelopment disorders.

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References

  1. Fact sheet for health care providers emergency use authorization (EUA) of REGEN-COV. https://www.fda.gov/media/145611/download. Accessed September 15, 2021.
  2. O’Brien MP. Forleo-Neto E, Musser BJ et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med 2021, August 4, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2109682

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the evidence that REGEN-COV (casirivimab and imdevimab) monoclonal antibody cocktail is effective in the post-exposure prophylaxis of Covid-19?

Should patients previously immunized against Covid-19 receive selected monoclonal antibodies when diagnosed with a breakthrough infection?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Although published studies supporting monoclonal antibody therapy in mild to moderate Covid-19 preceded availability of Covid-19 vaccines and the emergence of new variants of concern,1,2 given the possibility of severe breakthrough Covid-19 in high risk vaccinated patients with suboptimal immunity and the retained activity of certain monoclonal antibody products (ie, casirivimab and imdevimab-Regeneron-Cov and sotrovimab) against common variants of SARS-CoV-2 , their use is recommended even in vaccinated individuals with mild to moderate Covid-19.3-5

In fact, the CDC states that “For people who have received one or more doses of Covid-19 vaccine and subsequently experience SARS-CoV-2 infection, prior receipt of a Covid-19 vaccine should not affect treatment decisions (including use of monoclonal antibodies, convalescent plasma, antiviral treatment, or corticosteroid administration) or timing of such treatment.”3

In its July 30, 2021 Emergency Authorization Use (EUA) letter regarding use of casirivimab and imdevimab – REGEN-COV), the FDA does not distinguish between vaccinated and unvaccinated individuals for its indications,4 similar to those of guidelines posted by the Department of Health and Human Services and the NIH.5-6

When indicated, high risk vaccinated individuals with Covid-19 should be offered  an FDA approved (under EUA currently) monoclonal antibody product (such as  casirivimab and imdevimab antibody cocktail or sotrovimab) soon after diagnosis and certainly no later than 10 days.

Vaccinated individuals with mild to moderate Covid-19 not requiring hospitalization and for whom monoclonal antibody treatment may be indicated include older patients and those with risk factors for severe disease, such as obesity, pregnancy, chronic kidney disease, chronic lung disease (including COPD), immunocompromised state, serious heart conditions (eg, heart failure, coronary artery disease, cardiomyopathies), sickle cell disease and type 2 diabetes.7

Of note, casirivimab and imdevimab is indicated for adults (weighing at least 40 kg) and children 12 years or older and is administered by IV infusion or subcutaneously, if IV infusion is not feasible and would lead to delay in treatment.4

Bonus Pearl: Did you know that in phase III trials, casirivimab and imdevimab  antibody cocktail reduced hospitalization or death by 70% in non-hospitalized patients with Covid-19?2

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References

  1. Interim clinical considerations for use of Covid-19 vaccines currently authorized in the United States. 2021. Available at https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html. Accessed August 22, 2021.
  2. March 23, 2021 https://www.roche.com/media/releases/med-cor-2021-03-23.htm
  3. Dougan M, Nirula A, Azizad M, et al. Bamlanivimab plus Etesevimab in mild or moderate Covid-19. N Engl J Med, July 14, 2021. https://www.nejm.org/doi/10.1056/NEJMoa2102685
  4. Letter, EUA REGEN-COV, July 30, 2021. https://www.fda.gov/media/145610/download
  5. Department of Health and Human Services. High risk Covid-19 outpatients may avoid hospitalization with monoclonal antibody treatment. July 16, 2021. https://combatcovid.hhs.gov/sites/default/files/documents/High-Risk-COVID-19-Outpatients-072021.pdf
  6. Anti-SARS Cov-2 monoclonal antibodies. Accessed August 22, 2021. https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/anti-sars-cov-2-monoclonal-antibodies/
  7. Science brief: evidence used to update the list of underlying medical conditions that increase a person’s risk of severe illness from Covid-19. Accessed August 22, 2021. https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/underlying-evidence-table.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should patients previously immunized against Covid-19 receive selected monoclonal antibodies when diagnosed with a breakthrough infection?