Emergency Use Authorization for Lower Dose Intravenous and Subcutaneous Casirivimab Plus Imdevimab

On June 4, 2021, the dose of casirivimab and imdevimab monoclonal antibody cocktail authorized by the Food and Drug Administration (FDA) was lowered from 2400 mg to 1200 mg—600 mg of each agent administered as a single infusion or injection. This antibody combination is authorized for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients 12 years of age and older weighing at least 40 kilograms, or approximately 88 pounds.1,2 In addition to the lower dose intravenous (IV) infusion, the Emergency Use Authorization (EUA) now includes the addition of a subcutaneous (SC) injection of this dual-agent therapy.1,2

The updated EUA is supported by data from a phase 3 COV-2067 (NCT04425629) clinical trial of 4567 high-risk individuals with mild-to-moderate COVID-19.2 Data showed the risk of severe SARS-CoV-2 to be reduced by 70%, a 4-day shorter duration of symptoms, and significantly reduced viral load in nonhospitalized patients compared with placebo. Similar efficacy was observed with both the 2400 mg dose and the 1200 mg dose. The SC administration of casirivimab and imdevimab was authorized based on all clinical data, viral-load reduction, and pharmacokinetic evidence to date.1

In addition, in vitro studies report that casirivimab and imdevimab retain potency against viral variants circulating within the US, including those first identified in Brazil (P.1/gamma) and South Africa (B.1.351/beta).1,4

Infusion-related reactions of grade 2 or higher have been observed in 0.2% of people who have received IV therapy; 12% of those treated subcutaneously have experienced injection-site reactions.1 In May, the definition of eligible patients for outpatient COVID-19 monoclonal antibody therapies was expanded to include more medical conditions and other factors, such as race or ethnicity, that increase risk for severe disease.1

An ongoing Phase 3 study of casirivimab with imdevimab is investigating SC administration of this combination for prophylaxis in asymptomatic adults exposed to household contacts with SARS-CoV-2 infection. Preliminary data show reduced risk of symptomatic infections by 81%.5,6

References

  1. Food and Drug Administration (FDA). Fact Sheet for Health Care Providers Emergency Use Authorization (EUA) of REGEN-COV™ (casirivimab and imdevimab). https://www.fda.gov/media/145611/download. Accessed June 10, 2021.
  2. Coronavirus (COVID-19) update: June 4, 2021 (www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-june-4-2021) Accessed 6/11/2021.
  3. Safety, tolerability, and efficacy of anti-spike (S) SARS-CoV-2 monoclonal antibodies for the treatment of ambulatory adult and pediatric patients with COVID-19. NCT04425629 (https://clinicaltrials.gov/ct2/show/NCT04425629). Accessed 6/10/2021.
  4. World Health Organization. Tracking SARS-CoV-2 variants (www.who.int/en/activities/tracking-SARS-CoV-2-variants). Accessed 6/11/2021.
  5. COVID-19 study assessing the efficacy and safety of anti-spike SARS CoV-2 monoclonal antibodies for prevention of SARS CoV-2 infection in asymptomatic healthy adults and adolescents who are household contacts to an individual with a positive SARS-CoV-2 RT-PCR assay. NCT04452318 (https://clinicaltrials.gov/ct2/show/NCT04452318). Accessed 6/10/2021.
  6. Regeneron press release, 4/12/2021. Phase 3 prevention trial showed 81% reduced risk of symptomatic SARS-COV-2 infections with subcutaneous administration of REGEN-COV™ (casirivimab with imdevimab) (https://investor.regeneron.com/news-releases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars). Accessed 6/11/2021.
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Updates in the Treatment and Prevention of COVID-19​

Bebtelovimab Is the Only Monoclonal Antibody That Retains Activity Against Omicron Subvariants

The Omicron subvariants BA.2 and BA.2.12.1 now account for 99% of all COVID-19 cases in the United States. Studies assessing the neutralizing activity of monoclonal antibodies for the treatment of COVID-19 have found that only bebtelovimab retains activity against BA.2 and BA.2.12.1. Other monoclonal antibodies, including sotrovimab, bamlanivimab, etesevimab, casirivimab, and imdevimab, are not effective against these new subvariants and are not currently authorized by the US Food and Drug Administration (FDA) to treat COVID-19 due to the high incidence of Omicron BA.2.

Bebtelovimab is authorized for emergency use by the FDA for the treatment of mild-to-moderate COVID-19 in patients 12 years and older weighing at least 40 kg with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death. Bebtelovimab should be administered as soon as possible after positive SARS-CoV-2 results and within 7 days of symptom onset.

FDA Approves Baricitinib for Hospitalized COVID-19 Patients

Baricitinib, an oral Janus kinase (JAK) inhibitor, is now FDA-approved for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). It is also authorized for emergency use by the FDA for hospitalized pediatric patients between 2 and 18 years of age who require oxygen support. The approval of baricitinib is based on efficacy and safety data from the ACTT-2 and COV-BARRIER clinical trials. In ACTT-2, baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time, particularly in patients receiving high-flow oxygen or noninvasive ventilation (10 days vs 18 days; rate ratio for recovery, 1.51; 95% confidence interval (CI), 1.10 to 2.08). The 28-day mortality was 5.1% with baricitinib plus remdesivir and 7.8% with remdesivir alone (hazard ratio [HR] for death, 0.65; 95% CI, 0.39 to 1.09). The COV-BARRIER trial found that baricitinib, in addition to standard of care (SoC), was associated with reduced 28-day mortality in hospitalized adults with COVID-19 compared with SoC alone (8% vs 13%; HR, 0.57; 95% CI, 0.41 to 0.78; P= .0018). The 60-day all-cause mortality was 10% with baricitinib plus SoC versus 15% with SoC (P= .005).

References:
Baricitinib fact sheet for healthcare providers. May 2022. (https://www.fda.gov/media/143823/download).  Accessed 5.24.2022.

Baricitinib (Olumiant®) PI 2022 (https://pi.lilly.com/us/olumiant-uspi.pdf). Accessed 5.24.2022.

Bebtelovimab fact sheet for healthcare providers. May 2022. (https://www.fda.gov/media/156152/download).  Accessed 5.24.2022.

Centers for Disease Control and Prevention (CDC). COVID data tracker. May 23, 2022. (https://covid.cdc.gov/covid-data-tracker/#variant-proportions). Accessed 5.24.2022.

Iketani S, et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature. 2022;604:553-556.

Kalil AC, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384:795-807.

Marconi VC, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Resp Med. 2021;9:1407-1418.