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Regen-CoV for COVID-19

Physiology

  • The product is a combination of two monoclonal antibodies – (casirivimab and imdevimab) that bind to separate sites of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor.

Evidence

  • The phase 3 trial showed a reduction from 4.6% to 1.3% covid related hospitalization (71.3% relative reduction) and a reduction from 3.2% to 1.0% all-cause death (70.4% relative reduction). Both were found to be statistically significant. 
  • Median time to resolution of symptoms was 4 days shorter in the treatment group. 
  • Efficacy was consistent even for those with SARS-CoV2 antibodies.
  • Viral load dropped more rapidly in the treatment arm than in placebo. 
  • Infusion reactions were “infrequent” at a rate of <0.3%
  • Phase 1 data and phase 3 data are summarized by NIH in this table.
  • A separate Phase 3 trial of the SQ injection for post-exposure prophylaxis showed a reduction from 7.5% to 1.5% symptomatic COVID infection (81% relative reduction). 
  • Interestingly, it was more effective in weeks 2-4 after exposure, decreasing symptomatic covid from 3.6% to 0.3% (92.6% relative risk reduction).
  • 1137/1505 participants (75%) were met the FDA criteria for high risk. 

Authorized Use

  • It is approved for use in patients 12 years and older, weighing at least 40kg, with mild to moderate COVID-19 who meet the following criteria: (fact sheet)
    • Tested positive for COVID and are within 10 days of symptom onset AND
    • At high risk of progression to severe covid, which the CDC defines as :
      • Adults age >65
      • Adults with the following medical illnesses
        • Cancer
        • Chronic Kidney Disease (any stage)
        • Chronic Lung Disease (COPD, Asthma, Interstitial Lung Disease, Cystic Fibrosis, Pulmonary HTN)
        • Dementia or other neurological conditions
        • Diabetes (type 1 or 2)
        • Down Syndrome
        • Heart Conditions (CHF, CAD, Cardiomyopathy, HTN)
        • HIV
        • Immunocompromised State (Genetic disorders, prolonged use of steroids, chemotherapy, etc)
        • Liver disease (alcohol-related liver disease, nonalcoholic fatty liver disease, and especially cirrhosis, or scarring of the liver)
        • Overweight  (BMI >25 – <30) and obesity  (BMI >30 – <40) and severe obesity  (BMI >40)
        • Pregnancy and up to 42 days following pregnancy
        • Sickle cell disease or thalassemia
        • Smoking (current or former)
        • Solid organ or blood stem cell transplant
        • Stroke, cerebrovascular disease
        • Substance abuse disorders
      • Current evidence suggests that children with medical complexity, with genetic, neurologic, metabolic conditions, or with congenital heart disease can be at increased risk for severe illness from COVID-19. Similar to adults, children with obesity, diabetes, asthma or chronic lung disease, sickle cell disease, or immunosuppression can also be at increased risk for severe illness from COVID-19
  • Approval was also given for post-exposure prophylaxis of high risk patients (12 years and older, at least 40kg) who are  “not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications3) and
    • have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Center for Disease Control and Prevention (CDC) or
    • who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons)
  • It is NOT AUTHORIZED for use in patients: (fact sheet)
    • who are hospitalized due to COVID-19, OR 
    • who require oxygen therapy due to COVID-19, OR
    • who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity. 
    • Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. 

Dosing and Administration

  • Dosing is 600mg of casirivimab and 600 mg of imdevimab given as an infusion or a subcutaneous injection.  Repeat dosing for continued exposure, in a person who is not vaccinated or not expected to mount an immune response to vaccination, can be given every 4 weeks at half dose: 300mg of casirivimab and 300 mg of imdevimab
  • Duration of infusion depends on the volume and ranges from 20 minutes (50 ml) to 50 minutes (250 ml). (see table 3+4)
  • Observation for 1 hour is recommended after administration IV or SQ. 

Pregnancy and Lactation

  • There is no data regarding pregnancy or lactation. 

Adverse Reactions

  • In the phase 1/2/3 trials, adverse reactions occurred at a rate of 0.2% (10 patients out of 4206). 
  • Three subjects experienced urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, rash due to infusion. 
  • Anaphylactic reactions have been reported and occurred within 1 hour. 
  • SQ dosing showed localized injection site reactions in 12% of the treatment patients vs 4% of placebo.

Miscellaneous

  • The drug is recommended by the NIH in the COVID-19 Treatment Guidelines publication.
  • AFTER receiving this monoclonal antibody therapy, patients should wait 90 days before COVID vaccination. (CDC

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