Periodic Reporting for period 3 - MPX-RESPONSE (A clinical research network to improve the management of Monkeypox virus disease)
Période du rapport: 2024-08-05 au 2025-08-04
Mpox is an acute febrile rash illness caused by the mpox virus, often accompanied by symptoms such as fever, headache, or muscle aches. Before 2022, cases outside Sub-Saharan Africa were rare and typically travel-related, and onward transmission was limited. However, in May 2022, a global outbreak led the World Health Organization (WHO) to declare mpox a Public Health Emergency of International Concern (PHEIC). Although cases in particular declined in Europe and South America rapidly by late 2022, transmission persists, and a new clade has emerged in the Democratic Republic of Congo (DRC), leading to a renewed PHEIC declared in August 2024.
The MPX-RESPONSE project aims to:
1) deepen our understanding of mpox, including its transmission patterns, and the evolution of the disease (via the MOSAIC cohort; WP2).
2) Evaluate the efficacy and safety of different antiviral treatments through randomized clinical trials (RTCs) (UNITY, EPOXI and MOSA; WP3/WP4).
3) Enhance Europe’s preparedness for future health emergencies by testing innovative trial designs and facilitating data sharing across global studies
The MPX-RESPONSE project aims to:
1) deepen our understanding of mpox, including its transmission patterns, and the evolution of the disease (via the MOSAIC cohort; WP2).
2) Evaluate the efficacy and safety of different antiviral treatments through randomized clinical trials (RTCs) (UNITY, EPOXI and MOSA; WP3/WP4).
3) Enhance Europe’s preparedness for future health emergencies by testing innovative trial designs and facilitating data sharing across global studies
The MOSAIC cohort (WP2) provided comprehensive insights into the clinical and virological characteristics of mpox caused by the clade IIb variant. The study underscored the need for continued research and forms the basis of a clinical characterization protocol for the ongoing mpox outbreaks. Findings were published in the Clinical Infectious Diseases (early 2025), and sub-studies are underway to assess the long-term immune responses.
The EPOXI trial (WP3) was designed to evaluate the efficacy and safety of tecovirimat for mpox, with the goal of securing marketing authorization from the EMA. Despite regulatory approvals in eight EU countries and the initiation of patient recruitment in mid-2024, the trial was halted prematurely in summer 2025 following reports from the UNITY study indicating that the drug did not reduce time to lesion resolution. The results will be included in a pooled Individual Participant Data Meta-Analysis (IPDMA).
UNITY and MOSA (WP4) are two RCTs designed to assess the efficacy and safety of antiviral treatments for mpox in different global regions. UNITY focuses on Brazil, Argentina, and Switzerland, while MOSA is centered in sub-Saharan Africa, where the disease is endemic and a different clade of mpox is circulating. During RP3, UNITY successfully completed recruitment, enrolling 480 participants in its randomized arm. The database was locked in July 2025, and results were presented at the IAS 2025 conference in Kigali. The findings confirmed that tecovirimat did not improve lesion resolution or other clinical outcomes, aligning with results from other trials such as STOMP and PALM007. The open-label arm was closed in July 2025, and preparations for an IPDMA are underway, involving UNITY, STOMP, EPOXI, and PLATINUM trials.
In parallel, MOSA advanced significantly as a platform-adaptive trial, integrating brincidofovir as a new treatment arm following tecovirimat’s reported absence of efficacy. The first patient was enrolled in December 2024, with 33 participants recruited during RP3. The trial expanded its regulatory footprint to Uganda and Sierra Leone. MOSA also secured additional funding from Africa CDC, supplementing EU support.
The EPOXI trial (WP3) was designed to evaluate the efficacy and safety of tecovirimat for mpox, with the goal of securing marketing authorization from the EMA. Despite regulatory approvals in eight EU countries and the initiation of patient recruitment in mid-2024, the trial was halted prematurely in summer 2025 following reports from the UNITY study indicating that the drug did not reduce time to lesion resolution. The results will be included in a pooled Individual Participant Data Meta-Analysis (IPDMA).
UNITY and MOSA (WP4) are two RCTs designed to assess the efficacy and safety of antiviral treatments for mpox in different global regions. UNITY focuses on Brazil, Argentina, and Switzerland, while MOSA is centered in sub-Saharan Africa, where the disease is endemic and a different clade of mpox is circulating. During RP3, UNITY successfully completed recruitment, enrolling 480 participants in its randomized arm. The database was locked in July 2025, and results were presented at the IAS 2025 conference in Kigali. The findings confirmed that tecovirimat did not improve lesion resolution or other clinical outcomes, aligning with results from other trials such as STOMP and PALM007. The open-label arm was closed in July 2025, and preparations for an IPDMA are underway, involving UNITY, STOMP, EPOXI, and PLATINUM trials.
In parallel, MOSA advanced significantly as a platform-adaptive trial, integrating brincidofovir as a new treatment arm following tecovirimat’s reported absence of efficacy. The first patient was enrolled in December 2024, with 33 participants recruited during RP3. The trial expanded its regulatory footprint to Uganda and Sierra Leone. MOSA also secured additional funding from Africa CDC, supplementing EU support.
• MOSAIC demonstrated the value of harmonized observational data collection and standardized tools, now applicable to future PHEICs.
• EPOXI served as a real-world test case for EU pandemic preparedness, revealing regulatory and operational bottlenecks.
• UNITY showed the absence of efficacy of Tecovirimat and will contribute to the growing use of IPDMA in regulatory decision-making, addressing methodological and data-sharing challenges.
• MOSA’s platform-adaptive design allows rapid integration of new treatments and is a model for future outbreak response trials.
• EPOXI served as a real-world test case for EU pandemic preparedness, revealing regulatory and operational bottlenecks.
• UNITY showed the absence of efficacy of Tecovirimat and will contribute to the growing use of IPDMA in regulatory decision-making, addressing methodological and data-sharing challenges.
• MOSA’s platform-adaptive design allows rapid integration of new treatments and is a model for future outbreak response trials.