EMA Launches Review of Tecovirimat Effectiveness for Mpox

The European Medicines Agency (EMA) has initiated a review of Tecovirimat SIGA, also called TPOXX, a medicine used to treat mpox. This follows emerging clinical trial data suggesting a lack of effectiveness. 

The mpox virus is an orthopoxvirus, a class that includes the smallpox virus. 

Tecovirimat SIGA was originally approved in the US to treat smallpox. The EMA and the Medicines and Healthcare products Regulatory Agency in the UK authorized its use in January 2022, at the start of an mpox outbreak in Europe, for the treatment of smallpox, mpox, cowpox, and vaccinia complications following smallpox vaccination, in adults and children weighing at least 13 kg.

The drug is an oral medicine that interferes with a protein called VP37 found on the surface of orthopoxviruses, preventing them from reproducing normally and thus slowing the spread of infection. No other treatments are authorized for mpox or cowpox infections, which may in rare cases be fatal.

European Cases Linked With Risky Sexual Behaviors

Mpox is a zoonotic infection occurring mainly in West and Central Africa, with most cases in Europe before 2022 either imported from countries where mpox is endemic or from contacts with documented epidemiological links to imported cases. The outbreak in the EU and UK has been transmitted between humans mainly through sexual contact. It primarily affects gay, bisexual, or other men who have sex with men and who have multiple sexual partners, participate in group sex, or attend sex-on-premises venues. Transmission occurs primarily within interconnected sexual networks.

Symptoms of mpox typically appear 1-3 weeks after infection and include fever, headache, chills, physical weakness, lymph node swelling, back pain, and muscle aches, along with a distinct, fast-spreading papular rash on the skin and mucosal sores in the mouth, nose, throat, or digestive tract that then turn into fluid-filled vesicles. Mild-to-moderate symptoms usually last 2-4 weeks and are followed by full recovery, though some people develop permanent scars. During outbreaks, the case fatality of mpox ranges from 0% to 11%. People who are immunocompromised, including those with HIV infection or AIDS, are at a higher risk for severe disease. 

Exceptional Circumstances Approval During Outbreak

Approval for Tecovirimat SIGA was granted under “exceptional circumstances” provisions, based only on pharmacodynamic and pharmacokinetic studies, because the disease is rare and sporadic, so human studies were not available. A condition of such authorization is that the company marketing Tecovirimat SIGA is required to provide an annual update on benefits and risks.

The EMA’s review is a postauthorization procedure that involves a scientific assessment by the agency on behalf of the EU aimed at resolving issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In the case of Tecovirimat SIGA (tecovirimat), the review was initiated at the request of the European Commission.

The review follows publication of preliminary results from two clinical trials. In the randomized, placebo-controlled PALM007 trial involving 597 children and adults with laboratory-confirmed clade I mpox in the Democratic Republic of the Congo (DRC), results reported in April in The New England Journal of Medicine showed that the drug did not reduce the duration of mpox lesions (median time to resolution, 7 vs 8 days). The overall mortality among enrollees, regardless of whether or not they received the drug, was 1.6% — much lower than that generally reported in the DRC, but this was attributed to hospitalization and high-quality supportive care within the trial.

The other trial, STOMP, involved people from multiple countries with mild-to-moderate laboratory-confirmed or presumptive clade II mpox. Again, the active drug did not demonstrate efficacy in time to skin and mucosal lesion resolution compared with placebo.

The EMA said that similar results had recently been obtained from another study, UNITY, which also did not indicate faster skin lesion resolution on tecovirimat compared with placebo. Further analyses from ongoing or recently completed studies are still awaited and will also inform the EMA’s final assessment.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.