FDA Approvals, Highlights, and Summaries: Infectious Disease

February 24, 2021

Veklury (remdesivir)

Remdesivir is an antiviral agent that inhibits SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication. It was the first drug approved by the FDA for treating the SARS-CoV-2 virus infection. It is indicated for adults and pediatric patients aged 12 years and older who weigh at least 40 kg for treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization. An Emergency Use Authorization has also been issued for younger children.

Approval was based on data from the Adaptive COVID-19 Treatment Trial (ACTT). Final analysis included 1,062 hospitalized patients with advanced COVID-19 and lung involvement, showing that patients treated with 10 days of remdesivir recovered faster than similar patients who received placebo. Results showed that patients who received remdesivir had a 31% faster time to recovery compared with those who received placebo (P <.001). Specifically, the median time to recovery was 10 days in patients treated with remdesivir compared with 15 days in those who received placebo (P <.001). Patients with severe disease (n=957) had a median time to recovery of 11 days compared with 18 days for placebo. A statistically significant difference was not reached for mortality by day 15 (remdesivir 6.7% vs placebo 11.9%) or by day 29 (remdesivir 11.4% vs placebo 15.2%). ( N Engl J Med. October 8, 2020)

Lampit (nifurtimox)

Nifurtimox is an antiprotozoal agent that, until recently, was available as an orphan drug in the United States for Chagas disease (American trypanosomiasis) caused by Trypanosoma cruzi. Approval for Chagas disease is specifically for children and adolescents younger than 18 years who weigh at least 2.5 kg.

Approval for nifurtimox was based on the number of treated patients who became IgG antibody negative or who showed an at least 20% decrease in optical density on 2 different IgG antibody tests against antigens of T cruzi. ( PLoS Negl Trop Dis. January 7, 2021)

Inmazeb (atoltivimab/maftivimab/odesivimab)

Atoltivimab/maftivimab/odesivimab is a monoclonal combination that simultaneously binds to the glycoprotein on the Ebola virus surface and blocks attachment and entry of the virus on the host cell membranes. It is indicated for treatment of Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients, including neonates born to mothers who are reverse-transcriptase polymerase chain reaction positive for Zaire ebolavirus infection.

Ebanga (ansuvimab)

Ansuvimab is a recombinant human IgG1 monoclonal antibody that binds to the glycoprotein on the Ebola virus surface and blocks attachment and entry of the virus on the host cell membranes. It is indicated for treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to mothers who are reverse-transcriptase polymerase chain reaction positive for Zaire ebolavirus infection.

Rukobia (fostemsavir)

Fostemsavir, a prodrug of temsavir, is a first-in-class glycoprotein 120 (gp120) attachment inhibitor. It binds directly to the gp120 subunit on the surface of the virus, and thereby blocks HIV from attaching to host immune system CD4⁺ T cells and other immune cells. It is indicated in combination with other antiretroviral drugs for treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection in whom their current antiretroviral regimen failed owing to resistance, intolerance, or safety considerations.

Approval was based on the BRIGHTE study (n=371 [including 99 participants in the nonrandomized cohort]). All participants had a viral load of 400 copies/mL or greater and 2 or fewer classes of antiretrovirals remaining at baseline. On day 8, participants treated with fostemsavir (n=203) had a significantly greater decrease in levels of HIV-RNA in their blood compared with those taking the placebo (n=69) (0.79 vs 0.17 log10 copies/mL decline, respectively; P <.0001). After day 8, all participants received fostemsavir with other antiretrovirals. After 24 weeks of fostemsavir plus other antiretrovirals, 53% achieved HIV-RNA suppression, where levels of HIV were low enough to be considered undetectable. After 96 weeks, 60% continued to have HIV-RNA suppression. ( N Engl J Med. March 26, 2020;382(13):1232-1243)

Artesunate

Artesunate is an antimalarial artemisinin derivative. It is rapidly metabolized to the active metabolite, dihydroartemisinin (DHA). Artesunate and DHA, like other artemisinins, contain an endoperoxide bridge that is activated by heme iron that leads to oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and decreased parasite growth and survival. Artesunate and DHA are active against the blood-stage asexual parasites and gametocytes of Plasmodium species, including the chloroquine-resistant strains.

Artesunate is administered intravenously and is indicated for adults and children for initial treatment of severe malaria. It should always be followed by a complete treatment course of an appropriate oral antimalarial regimen.

Artesunate IV was officially approved by the FDA in May 2020 (it was previously available from the CDC through an Investigative New Drug protocol). Approval was based the South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) and the African Quinine Artesunate Malaria Trial (AQUAMAT). These 2 studies examined a total of 6886 patients and included adults, children, and pregnant women. Artesunate IV reduced mortality by 34.7% (P=.0002) and 22.5% (P=.002) compared with quinine in the SEAQUMAT and AQUAMAT studies, respectively. ( Lancet. August 27-September 2, 2005;366(9487):717-25; Lancet. November 13, 2010;376(9753):1647-57)

Emergency use authorizations (EUAs) issued for COVID-19

COVID-19 vaccine, mRNA-Pfizer (BNT-162b2) - 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 16 years and older

COVID-19 vaccine, mRNA-Moderna (mRNA-1273) - 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 and older

Bamlanivimab - EUA issued for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 2 years and 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 progressing to severe COVID-19 and/or hospitalization

Casirivimab/imdevimab - EUA issued for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 2 years and 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 progressing to severe COVID-19 and/or hospitalization

Baricitinib - EUA for use, in combination with remdesivir, for treatment of suspected or laboratory-confirmed coronavirus disease 2019 (COVID-19) in hospitalized patients aged 2 years and older who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation

Veklury (remdesivir) - EUA issued for antiviral treatment of coronavirus disease 2019 (COVID-19) in hospitalized pediatric patients weighing 3.5 kg to less than 40 kg or children younger than 12 years who weigh at least 3.5 kg

Other notable infectious disease approvals

Eraxis (anidulafungin) - Indication expanded to include children as young as 1 month for treatment of candidemia and other forms of candidal infections (intra-abdominal abscess and peritonitis)

Xofluza (baloxavir marboxil) - New indication approved for postexposure prophylaxis in persons aged 12 years and older following contact with an individual who has influenza; additionally, an oral suspension has been approved

Fetroja (cefiderocol) - Indicated for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible gram-negative microorganisms

Recarbrio (imipenem/cilastatin/relebactam) - New indication for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia

Dovato (dolutegravir/lamivudine) - New indication as a complete two-drug regimen for treatment of HIV infection in adults

Selzentry (maraviroc) - Indication expanded for treatment of only CCR5-tropic HIV infection to include patients weighing at least 2 kg

Prezcobix (darunavir/cobicistat) - Indication for treatment of HIV infection expanded to include patients weighing at least 40 kg

Evotaz (atazanavir/cobicistat) - Indication for treatment of HIV infection expanded to include patients weighing at least 35 kg

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: FDA Approvals, Highlights, and Summaries: Infectious Disease - Medscape - Feb 24, 2021.

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