EMA Reviews Tecovirimat Following Clinical Trial Data Showing Lack of Effectiveness Against Mpox
Key Insights
The European Medicines Agency (search) has initiated a comprehensive review of Tecovirimat SIGA following preliminary results from three clinical trials (PALM007, STOMP, and UNITY) that failed to demonstrate effectiveness in treating mpox (search) compared to placebo.
Tecovirimat was originally approved in January 2022 under exceptional circumstances based on animal studies and pharmacokinetic data, as human efficacy studies could not be conducted due to the sporadic nature of orthopoxvirus infections in the EU.
The EMA's Committee for Medicinal Products for Human Use will evaluate all available safety and effectiveness data to determine if regulatory measures are necessary for the continued use of this antiviral medication.
The European Medicines Agency (search) has launched a comprehensive review of Tecovirimat SIGA (tecovirimat) following emerging clinical trial data that questions the antiviral drug's effectiveness in treating mpox (search), the disease caused by the monkeypox (search) virus. The review comes after preliminary results from multiple studies failed to demonstrate clinical benefit over placebo treatment.
Clinical Trial Results Prompt Regulatory Action
Preliminary results from two completed studies, PALM007 and STOMP, both sponsored by the United States' National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, showed that patients with mpox (search) who received Tecovirimat SIGA did not recover from skin lesions faster than those who received placebo treatment. These findings were further supported by preliminary results from a third study, UNITY, which also failed to indicate faster skin lesion resolution compared to placebo in patients treated with tecovirimat.
The EMA noted that additional results and analyses from ongoing studies or recently completed ones, including PLATINUM-CAN, PLATINUM, and EPOXI trials, are still awaited and will inform the agency's assessment of the drug's therapeutic value.
Original Approval Under Exceptional Circumstances
Tecovirimat SIGA was authorized in January 2022 to treat mpox (search), smallpox (search) and cowpox (search) in adults and children weighing at least 13 kg. The drug received approval under 'exceptional circumstances' because mpox, smallpox and cowpox are either eradicated (smallpox) or occur sporadically in the EU, making it impossible to conduct traditional efficacy studies in infected people at the time of initial authorization.
The original approval was based on animal studies and pharmacodynamics and pharmacokinetics studies that examined the medicine's effects in the human body and how it is absorbed, modified and removed from the body in humans and animals. As a condition of the marketing authorization, Siga Technologies has been required to provide annual updates on the medicine's benefits and risks.
Mechanism of Action and Safety Profile
Tecovirimat SIGA works by interfering with a protein called VP37 (search) that is found on the surface of orthopoxviruses, including smallpox (search), monkeypox (search) and cowpox (search). By interacting with this protein, the medicine prevents the viruses from reproducing normally, slowing down the spread of infection.
Based on information available so far, there are no new safety concerns precluding the use of the medicine. The most common side effects with Tecovirimat SIGA are headache, which may affect more than 1 in 10 people, and nausea, which may affect up to 1 in 10 people.
Regulatory Review Process
The EMA's human medicines committee (CHMP) will now review all available data on the safety and effectiveness of Tecovirimat SIGA and make a recommendation on whether measures are necessary to ensure the safe and effective use of the medicine. The committee will thoroughly evaluate findings from ongoing studies alongside the previously completed trials to determine the drug's continued authorization status.
The review takes place against the backdrop of two public health emergencies of international concern declared by the World Health Organization in response to mpox (search) global outbreaks, which prompted several studies on the use of tecovirimat for mpox treatment both within the EU and internationally. The European Commission has not declared a public health emergency in Europe.
The EMA has indicated it will communicate further once the review has concluded, with the outcome potentially affecting the continued availability of this antiviral treatment for orthopoxvirus infections.