Will smallpox antivirals be effective against monkeypox?

Several cases of monkeypox, a rare viral disease marked by lesions, have been confirmed recently in a number of countries. So far, only one antiviral, tecovirimat, has been approved in any part of the world to treat monkeypox specifically. But existing treatments for smallpox, caused by a closely related virus, may also be effective.

Definitive data are limited. Smallpox was officially eradicated in 1980, so none of the three existing smallpox drugs have been tested in a human with smallpox.

A retrospective study published May 24 by Hugh Adler of the Liverpool School of Tropical Medicine and colleagues looked at the treatment of seven monkeypox cases in the UK from 2018 to 2021 (Lancet 2022, DOI: 10.1016/S1473-3099(22)00228-6), providing a glimpse of how these drugs might work.

Tecovirimat, sold under the brand name Tpoxx, is approved in Europe to treat several ailments, including monkeypox and smallpox. It is approved by the US Food and Drug Administration for smallpox. A small molecule manufactured by Siga Technologies, the drug works by inhibiting an envelope protein that the poxvirus needs to spread beyond an infected cell. Adler’s team showed that one patient treated with tecovirimat in 2021 had a shorter duration of illness than the other patients in the study.

Brincidofovir, sold as Tembexa, is also FDA approved for smallpox. It is a version of cidofovir—a different smallpox drug that is not FDA approved—with lipid moieties that improve oral bioavailability. Brincidofovir may also be safer than cidofovir. Both drugs inhibit the viral DNA polymerase, preventing DNA replication. In the Lancet study, brincidofovir was administered to three people with monkeypox, but treatment was stopped after they developed a recognized side effect.Emergent BioSolutions announced May 16 that it had bought the rights to Tembexa from Chimerix for $225 million.

Adler said on a call to discuss the study that his team saw promising signals in tecovirimat, but he emphasized that the sample size was small. “Our study should be seen as a springboard to bigger studies now in the current outbreak and especially studies in countries where monkeypox is endemic” he says.