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​

FDA Authorizes Lower Dose of Intravenous and Subcutaneous Dose of Casirivimab and Imdevimab Antibody Cocktail

The Food and Drug Administration authorized lower-dose (1200 mg) casirivimab and imdevimab monoclonal-antibody infusion therapy for nonhospitalized people with COVID-19 who have risk factors for disease progression. The Emergency Use Authorization (EUA) is supported by data from a phase 3 trial showing a consistent 70% reduced risk of hospitalization or death with either the lower dose or the higher dose (2400 mg) originally authorized. Subcutaneous administration of casirivimab and imdevimab was granted EUA based on scientific evidence to date regarding its safety and efficacy. 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.

This antibody combination has shown efficacy in vitro against variants of concern identified in the United States with origins from Brazil (P.1/Gamma) and South Africa (B.1.351/Beta).

In May 2021, 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 the risk for severe disease.

Subcutaneous Administration of Casirivimab and Imdevimab Reduced the Risk of Symptomatic COVID-19 by 81% Among Household Contacts

Top-line results from a phase 3 trial showed that the combination of casirivimab and imdevimab reduced the risk of symptomatic infections by 81% among household contacts of SARS-CoV-2 infected individuals. The trial enrolled 1,505 individuals who did not have COVID-19 symptoms or anti-SARS-CoV-2 antibodies, but who lived in the same household as an individual who tested positive for SARS-CoV-2 within the prior 4 days. A single subcutaneous injection of casirivimab and imdevimab provided rapid protection to those with exposure to SARS-CoV-2 at home, with protection against symptomatic infections ranging from 72% in the first week to 93% in subsequent weeks. Individuals who developed symptomatic infections despite casirivimab and imdevimab therapy had a shorter duration of symptoms compared with those who received placebo (1 week vs 3 weeks, respectively). Infected individuals who received therapy also cleared the virus faster. Adverse events (AEs) occurred in 20% of patients receiving casirivimab and imdevimab and 29% of patients receiving placebo. Injection site reactions, all of which were grades 1-2, occurred in 4% of patients in the treatment group and 2% of placebo participants.

Casirivimab and Imdevimab Significantly Reduced Progression to Symptomatic COVID-19 in Recently Infected Asymptomatic Patients

In a phase 3 trial of 204 recently infected asymptomatic COVID-19 patients, subcutaneous administration of casirivimab and imdevimab reduced the overall risk of progressing to symptomatic COVID-19 by 31%, and by 76% after the third day. In addition to reducing the risk of symptomatic infections, the top-line results report that the combination of casirivimab and imdevimab shortened the total number of weeks patients experienced symptoms by 45% and reduced the viral burden by more than 90%. No patients withdrew from the trial due to AEs in either group. Casirivimab and imdevimab are investigational drugs with emergency use authorization for the treatment of individuals with mild-to-moderate COVID-19 who are at high-risk of progressing to severe COVID-19 or hospitalization. Casirivimab and imdevimab (REGEN-COV™) continues to be evaluated in clinical trials in multiple settings for COVID-19, including the open-label RECOVERY trial of hospitalized patients in the UK.

Johnson & Johnson COVID-19 Vaccine Administration Paused

The Centers for Disease Control and Prevention (CDC) and the Federal Drug Administration (FDA) are recommending a pause in the use of the Ad26.COV2.S vaccine developed by Johnson & Johnson (Janssen) as they review data involving 6 reported cases of a rare and severe type of blood clot in individuals after vaccination. The vaccine has been administered to more than 6.8 million individuals in the US. In all 6 reported cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) occurred in combination with low platelet levels (thrombocytopenia). Treatment of CVST differs from other blood clots and administration of heparin may be dangerous in these patients. All 6 cases occurred among women aged 18 to 48 years and symptoms usually occurred 6 to 13 days after vaccination. People who develop severe headache, abdominal pain, leg pain, or shortness of breath within 3 weeks after vaccination should contact their healthcare provider.

References:

Regeneron Press Release. FDA Authorizes Lower 1,200 mg Intravenous and Subcutaneous Dose of REGEN-COV™ (Casirivimab and Imdevimab). Antibody Cocktail to Treat Patients with COVID-19. Available at: https://prnewswire.com/news-releases/fda-authorizes-lower-1-200-mg-intravenous-and-subcutaneous-dose-of-regen-cov-casirivimab-and-imdevimab-antibody-cocktail-to-treat-patients-with-covid-19–301305941

Regeneron Press Release. Phase 3 Prevention Trial Showed 81% Reduced Risk of Symptomatic SARS-CoV-2 Infections with Subcutaneous Administration of REGEN-COV™ (Casirivimab and Imdevimab). April 12, 2021. Available at: https://investor.regeneron.com/news-releases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars

Regeneron Press Release. Phase 3 Treatment Trial in Recently Infected Asymptomatic Patients Showed REGEN-COV™ (Casirivimab and Imdevimab) Significantly Reduced Progression to Symptomatic COVID-19. April 12, 2021. Available at: https://investor.regeneron.com/news-releases/news-release-details/phase-3-treatment-trial-recently-infected-asymptomatic-patients

FDA Statement. Joint CDC and FDA Statement on Johnson & Johnson COVID-19 Vaccine. April 13, 2021. Available at: https://www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccine