DSMB halts STOMP trial after finding Tpoxx gives no benefit for clade II mpox

The international Data and Safety Monitoring Board halted further enrollment in the NIH‑sponsored STOMP Phase 3 trial after an interim analysis found that a 14‑day course of oral tecovirimat (TPOXX) provided no clinical benefit for adults infected with clade II mpox. The decision followed randomization of 412 participants, 344 of whom had laboratory‑confirmed infection, across 49 sites in seven countries.

STOMP, also identified in trial registries as A5418 and NCT05534984, was designed as a double‑blind, randomized, placebo‑controlled study to test whether tecovirimat shortened the time to clinical resolution of all visible mpox lesions and improved secondary outcomes including pain and virologic clearance. The trial began in September 2022 as part of a coordinated U.S. outbreak response and enrolled adults who were nonpregnant, nonlactating and at low risk of severe disease; the CDC characterizes the randomized cohort as adults with clade IIb mpox without severe immunocompromise or severe infection.

The trialists report that tecovirimat did not reduce time to lesion resolution compared with placebo, did not lessen pain, and did not accelerate viral DNA clearance in the randomized population studied. NIAID summarized the interim data by saying that the antiviral drug “did not reduce the time to lesion resolution or have an effect on pain among adults with mild to moderate clade II mpox and a low risk of developing severe disease.” Investigators also found no major safety signals; tecovirimat demonstrated a favorable safety profile in this trial population, consistent with its prior widespread use under expanded access protocols.

The study incorporated an ethical rescue provision: at six days, participants with severe disease or severe pain could discontinue their blinded treatment and begin a 14‑day open‑label course of tecovirimat while initial group assignments remained blinded. As the trial authors wrote, “This rescue strategy, which allowed both placebo and tecovirimat recipients to switch to open‑label tecovirimat, was necessary to preserve blinding and because tecovirimat was the only widely available therapeutic option at the time that was considered to be safe.”

The STOMP findings align with results from PALM007, a randomized study in the Democratic Republic of the Congo testing tecovirimat for clade I disease; initial analyses from the two trials became available in August and December 2024 respectively, and both showed safety but no reduction in time to lesion resolution in their randomized cohorts. Timothy Wilkin, chief of infectious diseases and global public health at UC San Diego, said, “Since the start of the clade II outbreak, clinicians treating mpox have had limited evidence to guide their practice, and STOMP provided definitive answers on the lack of clinical utility of tecovirimat monotherapy for the randomized population studied.” He added, “Taken together, these latest results also highlight that we still have yet to isolate which factors influence mpox disease progression and clinical resolution.”

The broader clinical implications are immediate: for most patients without severe disease or risk factors for severe disease, the CDC says supportive care and pain management remain appropriate because most will recover without antiviral therapy. The agency recommends early tecovirimat for protracted or life‑threatening cases and for people at high risk from severe immunocompromise, and it notes combinations with cidofovir, brincidofovir, or Vaccinia Immune Globulin Intravenous may be reasonable in some high‑risk situations; however, the role of tecovirimat in severely immunocompromised patients, including those with advanced HIV, “has not been determined and requires additional clinical trials.”

Tecovirimat was previously approved by the FDA for smallpox based on animal efficacy data; until these randomized trials, evidence of benefit for mpox in humans had been limited to observational and expanded access use. Joseph Eron, chair of the AIDS Clinical Trials Group and chief of infectious diseases at the University of North Carolina, said, “The STOMP trial provides essential evidence at a critical time and demonstrates why randomized controlled trials are an indispensable part of outbreak response,” and added, “But now we must keep going to find safe and effective treatment for people as this virus continues to circulate globally.”