Tpoxx No Better Than Placebo for Clade I Mpox

The antiviral drug tecovirimat (Tpoxx) failed to shorten the duration of mpox lesions or lower mortality among children and adults with clade I mpox in the Democratic Republic of the Congo (DRC), according to results from the randomized, placebo-controlled PALM007 trial.

Among hospitalized patients with mpox, lesion resolution took a median of 7 days with tecovirimat compared with 8 days with placebo (competing-risks HR 1.13, 95% CI 0.97-1.31, P=0.14), and mortality was 1.7% in both groups by day 58 after randomization, reported Olivier Tshiani, MD, of Leidos Biomedical Research in Rockville, Maryland, at the annual IDWeek meeting in Los Angeles.

Mortality in the study was about half the 3.4% case fatality rate reported by the DRC, perhaps because of the supportive care patients received while hospitalized, he explained.

Also, investigators found no difference in time to lesion resolution between the two groups among patients treated within 7 days of symptom onset (competing-risks HR 1.16, 95% CI 0.98-1.37) or more than 7 days after symptom onset (competing-risks HR 1.00, 95% CI 0.71-1.40).

There was also no difference in mpox virologic resolution of infection with PCR testing between the intervention and placebo groups, regardless of anatomic sample site location (blood, lesion, oropharynx). By day 14, the vast majority of patients in both groups had resolution of their mpox lesions, Tshiani noted.

Tecovirimat is currently FDA approved only for the treatment of smallpox and is considered an investigational drug for the treatment of mpox. It is available only through the CDC’s expanded access investigational new drug (EA-IND) program or for people enrolled in the NIH-funded international STOMP trial, which is evaluating the efficacy and safety of tecovirimat against clade II mpox.

Following Tshiani’s presentation, Timothy Wilkin, MD, MPH, of the University of California at San Diego and protocol chair for the STOMP trial, discussed potential alternatives to tecovirimat for mpox treatment. “As we just learned, we have no current effective therapies” for mpox, he told attendees. “I think we’ve made the case that we need effective treatments … as we continue to have increasing cases globally and ongoing deaths.”

Those who are severely immunocompromised are most at risk, with a mortality rate of about 35% for untreated mpox-infected patients in that population, Wilkin noted.

Currently, the CDC recommends tecovirimat as a first-line treatment for severe mpox. If treatment fails to result in clinical improvement, the antiviral cidofovir (Vistide) or the cidofovir prodrug brincidofovir (Tembexa) and/or treatment with vaccinia immune globulin are recommended.

Although effective for smallpox, none of these therapies have been evaluated in clinical trials, Wilkin pointed out.

The PALM007 study evaluated the safety and efficacy of oral tecovirimat to treat mpox in combination with standard of care (SOC). The study enrolled patients with mpox from 2022 through 2024 from Tunda (Maniema Province) and Kole (Sankuru Province) in the DRC. There were no age restrictions, and patients were included if they weighed more than 3 kilograms and had at least one active mpox lesion and a PCR test positive for mpox. Patients were randomly assigned 1:1 to receive oral tecovirimat plus SOC (n=295) or placebo plus SOC (n=302) for 14 days. All patients were hospitalized for the entire 14-day course of treatment.

Standard of care included nutritional support, care of lesions, and psychological support, Tshiani told attendees. Tecovirimat dosing varied according to patient weight. Patients were followed for 29 days with an optional visit at day 59 for long-term assessment.

The mean age of study participants was about 16 years, about half were female, and over 64% were younger than age 18. The lesion count was extremely high, Tshiani said, averaging about 490 lesions in both the placebo and treatment groups. About 20% were coinfected with malaria, but very few (0.7%) were infected with HIV.