EUA Granted for Monoclonal Antibody for Hospitalized People With COVID-19

The monoclonal antibody, tocilizumab, blocks the interleukin-6 (IL-6) receptor and reduces inflammation caused by an overactive immune reaction to COVID-19. It was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) on June 24, 2021. The EUA applies to adults and pediatric patients hospitalized with COVID-19 and who are receiving systemic corticosteroids plus supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).1

The EUA is supported by four clinical trials—RECOVERY, EMPACTA, COVACTA, and REMDACTA—showing that tocilizumab plus standard of care reduced risk of death and decreased days spent in the hospital, with the most significant data emerging from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) and the EMPACTA (Evaluating Minority Patients with Actemra) trials of hospitalized patients with COVID-19 pneumonia.2-5

In the RECOVERY trial of 4,116 participants with hypoxia and evidence of systemic inflammation, the probability of death by day 28 was approximately 31% for those receiving tocilizumab (400 mg to 800 mg) plus standard of care compared with almost 35% of those receiving only standard of care. The median time to hospital discharge was also lower for those in the tocilizumab cohort; 19 days compared with more than 28 days for those only receiving usual care.2

In the EMPACTA trial of 389 participants belonging to underserved and racial and ethnic minority populations, there was a reduction in progression to mechanical ventilation or death for patients who received one or two doses of tocilizumab (8 mg/kg of body weight) compared with those who received placebo. Those who required mechanical ventilation or who died by day 28 was approximately 12% for the tocilizumab group and about 19% for those receiving placebo.3

References

  1. S. Food and Drug Administration (FDA). FDA News Release: Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19. Released June 24, 2021. Accessed July 15, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-treatment-covid-19.
  2. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645.
  3. Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with COVID-19 pneumonia. N Engl J Med. 2021;384:20-30.
  4. Rosas IO, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with severe COVID-19 pneumonia. N Engl J Med. 2021;384:1503-1516.
  5. A Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Participants With Severe COVID-19 Pneumonia (REMDACTA). Identifier: NCT04409262. Updated March 11, 2021. Accessed July 15, 2021. https://clinicaltrials.gov/ct2/show/NCT04409262
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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.