A recent study published in The New England Journal of Medicine (NEJM) evaluated the use of tecovirimat for monkeypox treatment during the current outbreak.
Human immunodeficiency virus (HIV) impacted some communities disproportionately in 1988 as it expanded quickly worldwide, especially among bisexual, gay, and other males who had sex with men. The world is currently dealing with a startlingly identical predicament 34 years later. An extraordinary monkeypox outbreak is currently overwhelmingly impacting males who have sex with men in several nations where the illness is not endemic, such as the United States (U.S.).
Monkeypox is not as fatal as HIV. Nonetheless, it can result in superinfections of soft tissues, ocular involvement, and insufferable anogenital lesions.
Tecovirimat, a drug currently available for clinical use within an expanded-access guideline, might theoretically quicken the resolution of monkeypox disease and improve outcomes. Nevertheless, its efficacy and safety in humans are unknown. Thus, the management of compassionate access to tecovirimat remains a problem.
The same virus genus causes monkeypox and smallpox. Hence, it is critical to comprehend the rationale behind the U.S. Food and Drug Administration (FDA) approval of tecovirimat in smallpox treatment and the knowledge gaps that still exist. Subsequently, this will help better understand the part tecovirimat may perform in the monkeypox outbreak.
About the study
In the present work, the researchers analyzed the previous, current, and potential future considerations of tecovirimat therapy for monkeypox based on its use in smallpox.
Tecovirimat in smallpox
The authors mentioned that the antiviral medicine tecovirimat was authorized for smallpox therapy under the Animal Rule. This approach enables the approval of medications for life-threatening ailments when it is impractical to perform field assessments to evaluate the potency of a biological product or drug in humans, as well as when it is not ethical to undertake efficacy investigations in humans.
Animal model studies with associated orthopoxviruses, specifically rabbitpox-infected rabbits and monkeypox-infected nonhuman primates, were used to determine the effectiveness of tecovirimat for smallpox treatment. Subsequently, the medication was approved. In these investigations, tecovirimat-treated animals had significantly greater survival rates than placebo-treated animals.
Safety among humans was estimated by monitoring adverse responses across healthy volunteers treated with tecovirimat. For establishing the optimal tecovirimat dose for smallpox treatment in humans, the studies compared the drug plasma levels among healthy subjects with those in animal models at doses proven to be fully effective against rabbitpox and monkeypox. The results of studies on healthy individuals and animals served as the foundation for the recommended length of tecovirimat therapy for humans during smallpox.
Tecovirimat in monkeypox
Monkeypox disease, unlike smallpox, is still prevalent in some regions of the world (mainly in Central and West Africa), and investigators were able to devise clinical studies that are both practical and ethical. Existing case reports illustrate tecovirimat usage for treating people infected with monkeypox and similar non-variola orthopoxviruses. Yet, there is not enough evidence to prove its effectiveness.
While animal research can be convincing, human efficacy in later clinical trials was not always correlated precisely with efficacy seen in animals. The team noted that people with monkeypox disease could provide safety data for tecovirimat instead of only healthy participants. Therefore, research on monkeypox in humans is both necessary and feasible.
To achieve this goal, before the current monkeypox outbreak, in the Democratic Republic of Congo (DRC), the National Institutes of Health (NIH) had begun preparing for a randomized, controlled trial (RCT) to assess the safety and effectiveness of tecovirimat in monkeypox therapy. The present global outbreak, however, encompasses a distinct monkeypox viral clade than that which typically infects people in the DRC. Moreover, some clinical manifestations of the current monkeypox outbreak and the communities affected at this time vary from those in nations where monkeypox is an endemic disease.
Hence, the NIH is presently developing a U.S.-centered RCT to evaluate the effectiveness and safety of tecovirimat for monkeypox treatment. The acquired immunodeficiency syndrome (AIDS) Clinical Trials Group will conduct this trial. The researchers expect these studies will offer the evidence required for clinical and regulatory decision-making in the U.S.
Overall, the team agrees that monkeypox can result in severe illness, and tecovirimat was effective against monkeypox in animal models and has a tolerable safety profile across healthy individuals. The FDA and Centers for Disease Control and Prevention (CDC) have collaborated to speed the expanded-access approach by minimizing paperwork and data collecting while RCTs were developing. Furthermore, the authors stated that they keep refining these mechanisms based on feedback from healthcare professionals.
Simultaneously, researchers believe it is essential to carry out RCTs in the U.S. to establish whether tecovirimat is an effective and safe monkeypox treatment, particularly in light of the disease's clinical manifestation during the present outbreak. Similar to HIV antiretrovirals in the 1980s, without information from RCTs, it will be challenging to determine if tecovirimat will be beneficial, harmful, or have no impact on monkeypox patients. The authors mentioned that the FDA, NIH, and CDC continue to collaborate to make tecovirimat available for compassionate use while adequately assessing its efficacy and safety in RCTs.