SIGA Technologies’ TPOXX did not outperform placebo at resolving lesions in patients with clade I mpox, the new strain that has spread through parts of Africa and is reaching beyond the continent.
SIGA Technologies’ antiviral drug TPOXX (tecovirimat) is safe but otherwise ineffective against clade I mpox, the cause of the current outbreak in Africa, according to a topline readout of the Phase II PALM007 trial.
In the study, nearly 600 patients with laboratory-confirmed mpox were given either TPOXX or placebo, in combination with the standard of care, and were admitted for 14 days. The study’s primary efficacy outcome was the number of days before all lesions on the body were scabbed or came off as flakes, and until a new layer of epidermis had formed.
Based on this metric, SIGA’s TPOXX was unable to significantly outperform placebo. At 28 days after randomization, lesion resolution remained statistically comparable between patients who were treated with the antiviral agent and those who received placebo.
Still, the biotech was optimistic about TPOXX’s role in the current outbreak, with Chief Scientific Officer Dennis Hruby saying that these topline data demonstrate “maximum benefit in patients treated early and with severe disease,” which is “entirely consistent with the mechanism action of tecovirimat.” SIGA maintains that these findings suggest that it is worth evaluating TPOXX further in this indication.
In terms of safety, PALM007 found that TPOXX’s adverse event profile was comparable to that of placebo, consistent with what had been established in prior studies.
PALM007, which is not a registrational study, is co-led by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and the Democratic Republic of Congo’s Institut National de Recherche Biomédicale.
TPOXX, administered either orally or intravenously, is an antiviral drug that works by targeting and disabling the VP37 envelope wrapping protein, which is displayed on the surface of orthopoxviruses and is important for their reproduction. TPOXX is approved for smallpox but was widely used off-label for mpox during the 2022 U.S. outbreak.
In September 2022, as case counts were climbing across the country, research from the University of California-Davis Health, published in the medical journal JAMA, suggested that the drug was effective against mpox, healing lesions in 40% of patients at day seven. By day 21, 92% of patients had healed lesions and were pain-free.
Given this potential, the U.S. Department of Health and Human Services in July 2024 signed a $113-million procurement option contract with SIGA to boost the country’s preparedness for future outbreaks.
The NIAID is also backing the STOMP trial, which is targeting to enroll more than 500 patients and will compare oral TPOXX to placebo. The study’s objective is to identify if TPOXX will accelerate the healing process and its impact on pain and disease progression.
