New COVID-19 Monoclonal Antibody Granted Emergency Use Authorization

On May 26, 2021, a new COVID-19 monoclonal antibody therapy—sotrovimab (previously VIR-7831)— was added to the list of infusion therapies authorized by the Food and Drug Administration for non-hospitalized people 12 years of age and older and weighing at least 40 kg, who have mild-to-moderate COVID-19 and risk factors for progressing to severe disease.1 Rather than binding to the angiotensin converting enzyme 2 (ACE2) receptor of the spike protein, sotrovimab binds to an epitope that is shared with the virus and is engineered to be highly concentrated in the lungs and to possibly enhance virus-specific T cell function.2,3  

The Emergency Use Authorization (EUA) of sotrovimab is supported by an interim analysis of the ongoing Phase 2/3 COMET-ICE clinical trial of 583 people who tested positive for COVID-19 and were then randomized to receive either 500 mg sotrovimab or placebo.1,4 Hospitalization or death occurred in 21 (7%) of the 292 people who received placebo, and in 3 (1%) of the 291 people who received sotrovimab.1

In vitro data indicates that sotrovimab is active against the variants originating from the United Kingdom (B.1.1.7), South Africa (B.1.351), Brazil (P.1), California (B.1.427/B.1.429), New York (B.1.526), and India (B.1.617).3 Potential side effects of sotrovimab include anaphylaxis, infusion-related reactions, rash, and diarrhea.1 Ongoing clinical studies of sotrovimab include COMET-PEAK and the planned COMET-TAIL and COMET-STAR trials.2,5 These studies are investigating the efficacy and safety of intramuscular (IM) sotrovimab in low-risk adults with mild-to-moderate COVID-19; early IM treatment of COVID-19 in high-risk adults; and IM-administered sotrovimab as prophylaxis for high-risk adults.2,5

Other COVID-19 monoclonal antibody infusion therapies with EUA include bamlanivimab plus etesevimab and REGN-CoV-2, which is a combination of casirivimab and imdevimab.6,7 The Centers for Disease Control and Prevention recently expanded the list of underlying medical conditions and characteristics associated with high-risk for severe COVID-19, making more people with COVID-19 eligible to receive these therapies.8

References

  1. US Food and Drug Administration (FDA). Coronavirus (COVID-19) Update: FDA authorizes additional monoclonal antibody for treatment of COVID-19. (fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19). Accessed 6/1/2021.
  2. GSK press release. Vir Biotechnology and GSK announce VIR-7831 reduces hospitalization and risk of death in early treatment of adults with COVID-19. (gsk.com/en-gb/media/press-releases/vir-biotechnology-and-gsk-announce-vir-7831-reduces-hospitalisation-and-risk-of-death-in-early-treatment-of-adults-with-covid-19) Accessed 6/1/2021.
  3. Fact sheet for healthcare providers—Emergency Use Authorization (EUA) of sotrovimab. (www.fda.gov/media/149534/download). Accessed 6/2/2021.
  4. COMET-ICE. VIR-7831 for the early treatment of COVID-19 in outpatients. NCT04545060 (https://clinicaltrials.gov/ct2/show/NCT04545060?term=NCT04545060&draw=2&rank=1) Updated 5/7/2021. Accessed 6/1/2021.
  5. COMET-PEAK. Safety, tolerability, and pharmacokinetics of second generation VIR-7831 material in non-hospitalized participants with mild to moderate COVID-19. NCT04779879 (https://clinicaltrials.gov/ct2/show/NCT04779879?term=NCT04779879&draw=2&rank=1) Updated 3/3/2021. Accessed 6/1/2021.
  6. Fact sheet for healthcare providers—Emergency Use Authorization (EUA) of bamlanivimab and etesevimab. (www.fda.gov/media/145802/download). Accessed 6/1/2021.
  7. Fact sheet for healthcare providers—Emergency Use Authorization (EUA) of REGEN-COV™ (casirivimab and imdevimab). (www.fda.gov/media/145611/download). Accessed 6/1/2021.
  8. Centers for Disease Control and Prevention (CDC). Medical conditions. (www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html). Accessed 6/1/2021.
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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.