FDA Drug Approvals, Infectious Disease — 2021 Midyear Review

August 20, 2021

Cabenuva (cabotegravir/rilpivirine) and Vocabria (cabotegravir)

Cabotegravir/rilpivirine is a combination of HIV-1 integrase strand transfer inhibitor (INSTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI), which are copackaged as 2 separate intramuscular (IM) injections. Cabotegravir/rilpivirine is indicated as a complete regimen for treatment of HIV-1 infection in adults to replace a current stable antiretroviral therapy regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. It is initiated as a once-monthly IM injection following lead-in therapy with oral cabotegravir (Vocabria) plus rilpivirine (Edurant) for a least 1 month.

The safety and efficacy of cabotegravir/rilpivirine were established through 2 randomized, open-label, controlled clinical trials in 1182 HIV-infected adults who were virologically suppressed (HIV-1 RNA <50 copies/mL) before initiation of the treatment. Patients in both trials continued to show virologic suppression at the conclusion of each study, and no clinically relevant change from baseline in CD4+ cell counts was observed. N Engl J Med. 2020 Mar 19;382(12):1112-1123; N Engl J Med. 2020 Mar 19;382(12):1124-1135

Tembexa (brincidofovir)

Brincidofovir is a prodrug of cidofovir. Brincidofovir effectively penetrates cells via its lipid conjugate, releasing the nucleotide analog cidofovir, which then acts to inhibit viral replication. Cidofovir diphosphate selectively inhibits orthopoxvirus DNA polymerase–mediated viral DNA synthesis by incorporation of cidofovir into the growing viral DNA chain. This results in reductions in the rate of viral DNA synthesis. It is indicated for treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.

The drug gained approval under the FDA's animal rule. Approval was based on efficacy data in 2 lethal orthopoxvirus animal models of human smallpox disease, the rabbit pox model (New Zealand white rabbits infected with rabbit pox virus) and the mouse pox model (BALB/c mice infected with ectromelia virus). In the pivotal studies in each model, brincidofovir resulted in statistically significant survival benefit versus placebo following delayed treatment after animals were infected with a lethal viral dose. Tembexa prescribing information

Infectious disease emergency use authorizations (EUAs)


Sotrovimab was granted an EUA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients aged 12 years or older who weigh at least 40 kg, with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

The phase 3 trial COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) demonstrated that sotrovimab significantly reduced the risk of hospitalization or death by 79% at day 29 among 1057 high-risk outpatients (P <.001). Day 29 analysis from COMET-ICE clinical trial.

Etesevimab (plus bamlanivimab)

Etesevimab was issued an EUA for use in combination with bamlanivimab for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years and older weighing at least 40 kg. Treatment is dependent on positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing in patients who are at high risk for progressing to severe COVID-19 and/or hospitalization.

NOTE: Owing to the increase in variants of concern (VOCs) in the United States, monoclonal antibodies that have gained EAU have been tested to evaluate activity against VOCs. As of March 24, 2021, US distribution ceased for bamlanivimab alone. On June 25, 2021, US distribution ceased for bamlanivimab plus etesevimab as the P.1/Gamma and B.1.351/Beta variants (first identified in Brazil and South Africa) exceeded 11% of cases throughout the United States. Consider use of casirivimab plus imdevimab or sotrovimab in outpatients who qualify for monoclonal antibodies.

In this arm of the phase 3 BLAZE-1 trial, the change in log viral load from baseline at day 11 was -3.72 for bamlanivimab 700 mg, -4.08 for bamlanivimab 2800 mg, -3.49 for bamlanivimab 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Among nonhospitalized patients with mild-to-moderate COVID-19 illness, treatment with bamlanivimab plus etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; however, no significant difference in viral load reduction was observed for bamlanivimab monotherapy. No difference in hospitalization rate was observed between bamlanivimab monotherapy or with the combination. Based on an analysis of available data, the authorized dosage regimen of the combination is bamlanivimab 700 mg plus etesevimab 1400 mg administered together as a single intravenous infusion.This regimen is expected to have similar clinical effects as the 2800-mg dosages evaluated in the study. JAMA . 2021;325(7):632-644

Ad26.COV2.S vaccine

Ad26.COV2.S vaccine was issued an EUA for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals aged 18 years or older.

This decision was based on the totality of scientific evidence, including data from the phase 3 ENSEMBLE study, which demonstrated that the vaccine was 85% effective in preventing severe disease across all regions studied and showed protection against COVID-19–related hospitalization and death, beginning 28 days after vaccination. N Engl J Med. 2021 Apr 21

Other infectious disease approvals

Natroba (spinosad) - New indication approved for scabies in adults and children aged 4 years and older.

Vaxchora (cholera vaccine) - Use for immunization against Vibrio cholera serogroup 01 expanded to include children aged 2 years and older.

Rapivab (peramivir) - Indication for acute uncomplicated influenza expanded to include children as young as 6 months.

BNT-162b2 (COVID-19 vaccine, mRNA-Pfizer) - Emergency use authorization for prevention of SARS-CoV-2 infection expanded to include adolescents aged 12 years and older.


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