Currently, there is no specific treatment approved for mpox. However, there are several antiviral medications used to treat smallpox and other conditions that may help patients with mpox. These antivirals include: tecovirimat or ST-246 (TPOXX); brincidofovir (Tembexa); and cidofovir (Vistide), an intravenously administered antiviral used to treat cytomegalovirus retinitis in patients with AIDS. Additionally, intravenous vaccinia immune globulin (VIGIV), which is licensed for the treatment of complications from smallpox (vaccinia) vaccination, may be authorized for use to treat mpox and other pox viruses during an outbreak. NIAID played a major role in the development of both tecovirimat and brincidofovir.
STOMP Trial in the U.S.
NIAID is conducting two clinical trials of tecovirimat specifically to treat patients with mpox. In September 2022, NIAID started a clinical trial of tecovirimat in the U.S. in collaboration with the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG). The trial will ultimately include more than 500 adults and children with mpox. Remote enrollment is now available: Volunteers may participate in this trial from anywhere within the United States. Those interested in enrolling can visit stomptpoxx.org for more information.
Adults with severe mpox or those at high risk for severe disease including individuals with underlying immune deficiency, a history of or active inflammatory skin conditions, pregnant people and children all will be enrolled in an open-label arm in which all participants receive tecovirimat. Other adult participants—530 total—will be randomly assigned in a 2:1 ratio to receive tecovirimat or placebo pills. Investigators will gather data to determine if participants receiving tecovirimat heal more quickly (all lesions scabbed over or flaked off) compared with those taking placebo.
PALM Trial in the Democratic Republic of Congo
NIAID and the National Institute for Biomedical Research (INRB) are conducting a separate clinical trial of tecovirimat in adults and children with mpox in the Democratic Republic of the Congo (DRC). This project was planned before the current multi-country outbreak of mpox. The trial is being conducted under PALM (short for “Pamoja Tulinde Maisha” a Kiswahili phrase that translates to “together save lives”), a government-to-government partnership between the U.S. and the DRC. PALM’s first study was the randomized controlled trial of multiple therapeutics for Ebola virus disease, which supported the regulatory approvals of the NIAID-developed mAb114 (Ebanga) and REGN-EB3 (Inmazeb) treatments.
NIAID funded preclinical studies of tecovirimat to determine its mechanism of action, safety, and efficacy. Subsequently, NIAID and the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, funded Phase 1, and Phase 2 clinical trials to test the safety and pharmacokinetics of an oral formulation of the investigational drug. The Food and Drug Administration (FDA) approved tecovirimat in 2018 for the treatment of smallpox in adults and children; and the drug has been added to the U.S. Strategic National Stockpile for use in the event of an outbreak. It is available in both an oral and intravenous formulation. Although the antiviral was only approved for the treatment of smallpox, its FDA approval was based on studies in nonhuman primates infected with monkeypox virus (mpxv).
NIAID also supported the early development of brincidofovir (Tembexa) as a treatment for smallpox. Similar to its support of tecovirimat, NIAID supported the discovery, preclinical development, and early clinical testing of the drug; BARDA funded its advanced clinical evaluation. The FDA approved brincidofovir for oral administration in 2021 as a smallpox treatment in adults and pediatric patients, including neonates based on animal efficacy data (rabbits infected with rabbitpox virus, and mice infected with ectromelia virus).
In addition to its work on these two medications, NIAID continues to screen other novel compounds to find potential antiviral candidates to treat mpvx and other pox viruses.