IDStewardship

Sotrovimab (Xevudy)

Sotrovimab photo

NOTICE: Information on COVID-19 therapies is rapidly changing. Information and links on this page may be rendered inaccurate as this occurs. 

KEY POINTS

  • On May 26, 2021 the US FDA released an Emergency Use Authorization (EUA) for sotrovimab (Xevudy, VIR-7831), which is a monoclonal antibody for COVID-19
    • EUAs are temporary and are eventually retracted
  • Wondering how sotrovimab got its name? Dr. Boden from Kaleio Brands breaks it down as follows…
    • Sotrovimab is a new monoclonal antibody from GlaxoSmithKline that was just recently named by the USAN Council and WHO’s INN Expert Group as part of the expedited naming pathway for products to treat COVID-19.  The official INN definition is:
      • immunoglobulin G1-kappa, anti-[Homo sapiens severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, receptor binding domain (RBD)], Homo sapiens monoclonal antibody
    • As a monoclonal antibody, the name utilizes the –mab stem, which is defined for monoclonal antibodies.  The –vi- infix indicates that this is an antiviral antibody.  The prefix sotro- is intended to distinguish the name from the nearly 11,000 nonproprietary names that have been assigned to drugs throughout the years.  There are 11 drugs whose names begin with the s-o-t letter combination and only 1 other drug begins with s-o-t-r (sotrastaurin).  At Kaleio, when we think about branding-like practices for nonproprietary names we have to be extremely creative and subtle, because the prefix is supposed to be devoid of meaning.  However it is not a stretch to imagine that the name,sotrovimab, was created in a way that evokes a sense of community or togetherness.  In fact, the sotro- prefix is evocative of the Spanish word for “we,” or nosotros. 
  • Mechanism: Sotrovimab is a recombinant human IgG1-kappa mAb that binds to a conserved epitope on the spike protein receptor binding domain of SARS-CoV-2 with a dissociation constant KD = 0.21 nM) but does not compete with human ACE2 receptor binding (IC50 value >33.6 nM [5 μg/mL]). Sotrovimab inhibits an undefined step that occurs after virus attachment and prior to fusion of the viral and cell membranes. The Fc domain of sotrovimab includes M428L and N434S amino acid substitutions (LS modification) that extend antibody half-life, but do not impact wild-type Fc-mediated effector functions in cell culture.
    • Monoclonal antibodies are a form of passive immunity
    • The activity of monoclonal antibodies for SARS-CoV-2 can vary by variant
    • Using the the  Fact Sheets for Healthcare Providers (data extracted 6/30/2021), here is a comparison of variant activity and monoclonal antibodies for COVID. See fact sheets for full details.
Reduction in susceptibility for variants and COVID-19 monoclonal antibodies comparison chart

Lineage with Spike Protein Substitution

 Origin Key Substitutions Tested Sotrovimab Casirivimab/Imdevimab Bamlanivimab-Etesevimab

B.1.117

UK

N501Y

No change

No change

No change

B.1.351

S. Africa

K417N+ E484K+ N501Y

No change

No change

215

P.1

Brazil

K417T+ E484K+ N501Y

No change

No change

>46

B.1.427/ B.1.429

California

L452R

No change

No change

9

B.1.526

New York

E484K

No change

No change

31
B.1.617 India L452R+ E484Q No change Not Reported

Not Reported
  • Criteria for qualifying per EUA includes: having mild-to-moderate COVID-19, being 12 years of age or older, weighing at least 40 kg, having a positive direct SARS-CoV-2 viral test, being within 10 days of symptom onset, and being at high risk for progression to severe COVID-19 (including hospitalization or death)
    • Not authorized for people who are hospitalized due to COVID-19, require oxygen therapy due to COVID-19, or have an increase in baseline oxygen flow rate due to COVID-19 (in people who are already on oxygen at baseline)
    • Qualifying criteria for “at high risk” for progression to severe COVID-19 is broad, see CDC webpage here and the sotrovimab Healthcare Provider Fact Sheet for full details
    • May worsen the patient’s condition if given too late in the course of the disease (i.e., to patients requiring hospitalization on high flow oxygen or mechanical ventilation)
    • The Fact Sheet for Patients and Caregivers must be supplied to the patient/caregiver as part of the EUA
    • The patient/ caregiver must be agreeable to the therapy as part of the EUA
  • Authorized dose is 500 mg given IV over 30 minutes
  • Comes as one dose per one vial and must be diluted in NS prior to being given
    • As part of the mixing process, need to let the vial come to room temperature over approximately 15 minutes after removal from the refrigerator
    • The manufacturer states “Do not invert the infusion bag“
    • Stable at 4 hours room temperature or 24 hours refrigerated after mixing
  • 60 minute post-infusion monitoring is required
  • May cause infusion-related reactions (e.g., fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia, chest pain, weakness, altered mental status, nausea, headache, hypotension, hypertension, angioedema, throat irritation, rash, pruritus, myalgia, dizziness)
    • As part of the EUA, medication errors and serious adverse events (e.g., death, inpatient hospitalization) must be reported to FDA Medwatch within 7 calendar days of onset of the event
  • The price of sotrovimab is likely to be similar to what the US government paid for casirivimab/imdevimab and bamlanivimab/etesivimab, which is from $1,250 a dose to $2,100 a dose

RESOURCES

 

Recent