NIH study shows limited effect of tecovirimat on mpox

The US National Institutes of Health (NIH) announced that tecovirimat, marketed as TPOXX by SIGA Technologies, did not significantly reduce the duration of mpox lesions in patients with clade I mpox in the Democratic Republic of the Congo (DRC). This announcement caused SIGA shares to plummet by over 19% on Thursday. The findings are part of the PALM007 study and come just a day after the World Health Organization (WHO) declared another mpox public health emergency. This is the second such emergency in two years, amid a surge of cases in the DRC and other African countries, with the potential for global spread.

The PALM007 study was co-sponsored by the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and the DRC's Institut National de Recherche Biomédicale (INRB). It enrolled 597 patients with laboratory-confirmed mpox who were randomly assigned to receive either tecovirimat or a placebo. Participants were then monitored in-hospital for two weeks. According to the NIH, tecovirimat did not outperform the placebo in accelerating the resolution of mpox lesions. However, the study observed a mortality rate of 1.7%, regardless of whether patients received tecovirimat or not. This rate is significantly lower than the typical 3.6% or higher mortality rate seen in mpox cases in the DRC, suggesting that high-quality supportive care played a crucial role in improving patient outcomes.

Jeanne Marrazzo, director of NIAID, described the results as "disappointing" but emphasized that the findings would provide essential information and highlight the need to identify other therapeutic candidates for mpox. She added that ongoing research on tecovirimat use in other populations with mpox would continue. Marrazzo reaffirmed the commitment to developing safe and effective interventions, including treatments and vaccines.

Tecovirimat was initially developed and approved by the FDA to treat smallpox, a more severe virus related to mpox. However, its safety and effectiveness in treating mpox remain unproven. Since a multi-country outbreak led to an initial WHO emergency declaration in mid-2022, two smallpox vaccines have been used to prevent mpox infection. Chief among these is Bavarian Nordic's third-generation vaccine Jynneos, which is FDA-approved and was commercially launched in the US for mpox this past April.

Further analyses of the PALM007 data are planned to determine whether certain subgroups, such as those who enrolled earlier or had more severe disease, may have benefited from tecovirimat. Lori Dodd, NIAID's PALM project lead for the DRC, stated that they would continue to evaluate the trial data to see if additional studies of tecovirimat in specific patient subgroups are warranted.

Meanwhile, research on tecovirimat is continuing through other studies. The STOMP trial is assessing the drug's efficacy against clade II mpox, a variant that tends to result in milder disease and was responsible for the global outbreak in 2022. Additionally, the UNITY study is evaluating tecovirimat in Argentina, Brazil, and Switzerland with a similar focus.

In conclusion, the recent findings from the PALM007 study indicate that tecovirimat does not significantly reduce the duration of mpox lesions. However, the lower-than-expected mortality rate suggests that supportive care plays a crucial role in patient outcomes. Ongoing and future research will continue to explore the potential of tecovirimat and other therapeutic candidates in treating mpox.