Monoclonal antibody combination approved for mild/moderate COVID-19

Health Canada has issued an Interim Order authorization for casirivimab and imdevimab for the treatment of mild to moderate COVID-19 in adults and adolescents (≥ 12 years of age, weighing at least 40 kg) who are at high-risk for progressing to hospitalization and/or death.1,2 Interim authorization for the monoclonal antibody combination was granted pending the results of trials to verify the clinical benefits of this therapy. Early clinical trial results suggest that the drug combination reduces the rate of COVID-19-related hospitalization or death by about 70%.2 Patients considered to be at high risk of contracting severe COVID-19, and therefore potential candidates for casirivimab and imdevimab, include those with one or more of the following risk factors: ≥ 50 years of age, irrespective of comorbidities ≥ 18 years of age and one of the following comorbidities: obesity, cardiovascular disease (including hypertension), chronic lung disease, diabetes, chronic kidney disease, chronic liver disease, or immunosuppression.2 Casirivimab and imdevimab are not authorized for use in patients who are hospitalized due to COVID-19, those who require oxygen therapy due to COVID-19, or patients on chronic oxygen therapy (due to underlying non-COVID-19 related comorbidity) who require an increase in baseline oxygen flow rate due to COVID-19. Monoclonal antibodies, such as casirivimab and imdevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation.2 Action Casirivimab and imdevimab are two recombinant human monoclonal antibodies that target the spike protein of SARS-CoV-2. Casirivimab and imdevimab bind to the spike protein and block its interaction with angiotensin-converting enzyme 2 (ACE2), leading to inhibition of infection of host cells.2 Dosage Casirivimab and imdevimab are administered together by intravenous (IV) infusion. The combination should be given as soon as possible after the onset of symptoms and after a positive result is obtained using a direct SARS-CoV-2 validated testing method to confirm the diagnosis of COVID-19.2 The recommended dosage for adults and adolescents (≥ 12 years of age, weighing at least 40 kg) is 1200 mg of casirivimab and 1200 mg of imdevimab given together as a single IV infusion (after dilution in a 250 mL bag of 0.9% sodium chloride injection). The infusion is administered over at least one hour (maximum infusion rate 270 mL/hr).2 Adverse effects Serious hypersensitivity reactions, including anaphylaxis, have been reported. Patients should be monitored during the infusion and for at least one hour after the infusion ends. Signs and symptoms of infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash (including urticaria), pruritus, myalgia, dizziness, fatigue and diaphoresis. If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care. The monoclonal antibody combination should only be administered in settings where there is immediate access to medications to treat a severe infusion reaction or anaphylaxis.2 Product information for casirivimab and/or imdevimab warns that circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies.2 Drug interactions No interaction studies have been performed. However, casirivimab and imdevimab are not renally excreted or metabolized by CYP450 enzymes. As a result, interactions are unlikely to occur with concomitant medications that are renally excreted or that are substrates, inducers or inhibitors of CYP450 enzymes.2 Supplied/Storage Casirivimab and imdevimab are expected to be available from Hoffmann-La Roche in July 2021. They will be supplied in cartons containing two single-dose vials per package: one vial of 1332 mg/11.1 mL of casirivimab and one vial of 1332 mg/11.1 mL imdevimab, or one vial of 300 mg/2.5 mL of casirivimab and one vial of 300 mg/2.5 mL imdevimab. Both products should be stored in the refrigerator (2°C to 8°C) in the original carton to protect from light.2 Other monoclonal antibodies approved or under consideration for COVID-19 Bamlanivimab for injection (Eli Lilly), an anti-SARS-CoV-2 spike protein monoclonal antibody, received interim authorization by Health Canada on Nov. 20, 2020. It is indicated for the treatment of adults and adolescents (≥ 12 years of age, weighing 40 kg or more) with mild to moderate COVID-19, who are at high risk of progressing to severe COVID-19 illness and/or hospitalization.3 In late April 2021, Health Canada issued an advisory warning about the potential risk of bamlanivimab treatment failure due to circulation of resistant SARS-CoV-2 variants. The drug showed reduced in vitro activity against SARS-CoV-2 variants with the E484K (e.g., South Africa or Brazil origin) and L452R (e.g., California origin) mutations. As a result, healthcare professionals are advised to take the epidemiology of variants into consideration before empiric use of bamlanivimab as single monoclonal antibody therapy, and to use bamlanivimab only in regions where there is a known or confirmed low prevalence of lineages containing E484K and/or L452R SARS-CoV-2 variants.4 Other monoclonal antibodies currently under consideration for approval by Health Canada include regdanvimab (Celltrion HealthCare), leronlimab (CytoDyn), bamlanivimab and etesevimab (Eli Lilly) and sotrovimab (GlaxoSmithKline).5 More detailed information on some of these monoclonal antibodies is freely available from The Medical Letter.6 References 1. Hoffmann-La Roche Ltd. Health Canada grants Interim Order authorization for casirivimab and imdevimab for the treatment of mild to moderate COVID-19. https://www.newswire.ca/news-releases/health-canada-grants-interim-order-authorization-for-casirivimab-and-imdevimab-for-the-treatment-of-mild-to-moderate-covid-19-812156971.html (accessed June 17, 2021). 2. Hoffmann-La Roche Ltd. Casirivimab and imdevimab for injection (casirivimab and imdevimab) product monograph. Mississauga, ON; June 9, 2021. https://pdf.hres.ca/dpd_pm/00061474.PDF (accessed June 17, 2021). 3. Eli Lilly Canada Inc. Bamlanivimab for injection product monograph. Toronto, ON; April 14, 2021. https://pdf.hres.ca/dpd_pm/00060539.PDF (accessed June 17, 2021). 4. Health Canada. Bamlanivimab - potential risk of treatment failure due to circulation of resistant SARS-CoV-2 variants. https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2021/75503a-eng.php (accessed June 17, 2021). 5. Health Canada. Drug and vaccine authorizations for COVID-19: list of applications received. https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/authorization/applications.html (accessed June 17, 2021). 6. Anon. Drugs for COVID-19. Med Lett Drugs Ther 2021; June 17. https://secure.medicalletter.org/drugs-for-covid-19 (accessed June 17, 2021)

Monoclonal antibody combination approved for mild/moderate COVID-19

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