FDA Drug Approvals, Infectious Disease — 2020 Midyear Review

August 14, 2020

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 because of 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 2020 Mar 26;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 2005 Aug 27-Sep 2;366(9487):717-25

Lancet 2010 Nov 13;376(9753):1647-57)

Other infectious disease approvals

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

Remdesivir - FDA granted an emergency use authorization for remdesivir to treat hospitalized patients with suspected of confirmed SARS CoV-2 infection and severe COVID-19 disease.

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