To curb the monkeypox epidemic in both endemic areas in Africa and elsewhere, the effectiveness of existing treatments, vaccines, and vaccination strategies needs to be evaluated and efforts improved to make vaccination and treatment available to all affected groups and regions, authors of a review article conclude. In the U.S., this includes prevention with vaccines and treatment with tecovirimat and brincidofovir.
“The vaccines available for dealing with the current outbreak are ACAM2000 and MVA-BN,” the authors write. “ACAM2000 (Emergent BioSolutions) is a second-generation live, attenuated vaccinia virus vaccine with Food and Drug Administration (FDA) approval for use before or after exposure to monkeypox. It is effective but associated with a risk of cardiac complications. MVA-BN is a third-generation live, attenuated, nonreplicating, modified vaccinia Ankara vaccine developed by Bavarian Nordic. The vaccine is approved for smallpox prevention in the United States and Europe and was licensed by the FDA in 2019 for monkeypox prevention. LC16m8 (KM Biologics), a third-generation, highly attenuated vaccinia virus vaccine, is also licensed for use against smallpox, but it is not currently authorized for monkeypox prevention.”
Tecovirimat, approved in the U.S. for the treatment of smallpox, acts through inhibition of the orthopoxvirus protein p37, which blocks cell-to-cell viral transmission. The authors report that data supporting the drug’s use for monkeypox come from preclinical studies, including 4 pivotal studies in nonhuman primates, phase 1 and 2 trials focused on safety and adverse effects, and a very small observational study that suggests the agent reduces the duration of viral shedding and illness.
A viral DNA polymerase inhibitor, brincidofovir has been tested in clinical trials of patients with cytomegalovirus disease after hematopoietic stem-cell transplants. It has gastrointestinal and hepatic toxic effects and a safety profile inferior to that of tecovirimat.
“Randomized clinical trials are needed to evaluate the efficacy of these drugs, regardless of their authorization status,” the authors write. “The WHO and several countries are implementing such trials, especially with tecovirimat. This evaluation should be performed not only in the countries affected by the current outbreak but also in areas where the disease is endemic. Availability for second-line treatment may be important, given the potential occurrence of resistance with first-line treatments.”