Clinical Treatment of Mpox

Treatment options

Overview

Currently there is no treatment approved specifically for monkeypox virus (MPXV) infections. For most patients with mpox who do not have severe disease or risk factors for severe disease (e.g., severe immunocompromise), supportive care and pain control will help them recover.

However, some patients have experienced severe manifestations of mpox, including:

• Ocular infections
• Neurologic complications
• Myopericarditis
• Complications associated with mucosal (oral, rectal, genital, and urethral) lesions
• Complications from uncontrolled viral spread due to moderate or severe immunocompromise, particularly advanced HIV infection

Patients who are severely immunocompromised or have certain skin conditions, such as eczema, are at particular risk of uncontrolled viral spread, which can be life-threatening.

Interim clinical guidance developed by CDC may assist clinicians in managing patients with protracted or life-threatening manifestations of mpox. Treatment for these patients involves Food and Drug Administration (FDA)–regulated drugs and biologics that are primarily stockpiled by the U.S. government.

Available therapeutics

Tecovirimat (also known as TPOXX, ST-246)

Tecovirimat is an antiviral that was made available for treatment of certain patients with mpox under the CDC-held Expanded Access-Investigational New Drug (EA-IND) protocol during the global outbreak of mpox that began in 2022.

The compassionate use of tecovirimat was based on the animal efficacy data that showed survival benefit over placebo in lethal animal models. While it may be reasonable to anticipate that tecovirimat may provide benefit in treating some people with mpox, it was unknown whether and how the efficacy in animals may translate to humans with active disease. Randomized clinical trials were launched in 2022 to evaluate the efficacy and safety of tecovirimat in people with mpox.

Information from clinical trials

Interim analysis data from two clinical trials (PALM007 and STOMP), sponsored by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID), to evaluate the safety and efficacy of tecovirimat in persons with mpox became available in August and December of 2024, respectively. They showed that while tecovirimat was safe, it did not reduce the time to resolution of mpox lesions among participants who were randomized to receive tecovirimat or placebo.

Tecovirimat (TPOXX) study results from Democratic Republic of the Congo (PALM007)

PALM007 trial (NCT05559099) was launched in October 2022 by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), and the Democratic Republic of the Congo (DRC)'s National Institute for Biomedical Research to examine the safety and efficacy of tecovirimat for clade I mpox treatment in adults and children. The randomized, placebo-controlled study enrolled 597 people with laboratory-confirmed mpox at two sites in the DRC. Study participants were randomly assigned to receive tecovirimat or placebo and were admitted to a hospital for at least 14 days, where they were monitored closely for safety and resolution of mpox lesions. All participants received supportive care including nutrition, hydration, and treatment for secondary infections.

Initial analyses released in August 2024 indicated that tecovirimat did not reduce the duration of mpox lesions among children and adults with clade I mpox in DRC. However, the study's 1.7% overall mortality was much lower than the mpox mortality of 3.6% or higher reported among cases looked at together across all of the DRC, showing that better outcomes among people with mpox can be achieved when they are hospitalized and provided high-quality supportive care. The hospitalization ensured serial specimens could be collected (e.g. blood and lesion swabs) and the patients could be monitored closely for lesion resolution as well as be provided with the adequate nutrition needed for TPOXX absorption, fluids and pain-relief. Within the DRC, these basic healthcare needs are lacking within some parts of the country.

Tecovirimat was well-tolerated with no drug-related serious adverse events, and due to the supportive care patients received, lesions resolved faster than anticipated regardless of whether participants received tecovirimat or placebo. Additional analyses are planned to better understand outcomes observed in the study, including whether there were any significant differences in clinical outcomes by days of symptoms prior to enrollment, severity of clinical disease, participant characteristics, or the genetic variant of mpox being treated.

Tecovirimat (TPOXX) study results from the Study of Tecovirimat for Mpox (STOMP)

The STOMP trial (NCT05534984) was launched in September 2022 by NIH/NIAID as part of the U.S. whole-of-government response to the clade II mpox outbreak. The randomized international efficacy study enrolled participants who had been ill with mpox for less than 14 days in Argentina, Brazil, Japan, Mexico, Peru, Thailand, and the United States, including Puerto Rico. Participants were randomized at a two-to-one ratio to receive tecovirimat or a placebo. Randomized participants and investigators were blinded, meaning they did not know who received tecovirimat or placebo. Children, pregnant people, and other participants with severe disease, certain skin conditions, or substantially suppressed immune systems were assigned to an open-label study arm, meaning they all received tecovirimat instead of being randomized. The STOMP study assessed all participants' safety and, in randomized arms, evaluated whether a 14-day course of tecovirimat reduced the time to clinical resolution of visible mpox lesions and improved other outcome measures like pain, compared to a placebo.

Initial analyses released in December 2024 indicated that tecovirimat did not reduce the time to resolution of mpox lesions or have an effect on pain among adults with mild to moderate clade II mpox and a low risk of developing severe disease. STOMP-randomized study participants were non-pregnant and non-lactating adults with clade IIb mpox who did not have severe immunocompromise or severe mpox in the U.S. and other countries.

The role of tecovirimat in treatment of mpox in patients with severe immunocompromise, including advanced HIV, has not been determined and requires additional clinical trials.

Tecovirimat access for treatment in certain patients with mpox

Tecovirimat from the Strategic National Stockpile (SNS) will remain available for treatment of mpox in patients who have or are at high risk for severe illness as defined in the CDC-held expanded access IND protocol. Those at high risk include people who:

• Are severely immunocompromised patients (e.g., those with HIV with CD4 <200, or solid organ transplant recipients)
• Have atopic dermatitis and other conditions affecting skin integrity
• Are children
• Are pregnant or breastfeeding

Additional therapeutics

Tecovirimat is typically the first therapeutic that is considered if patients with mpox require more than supportive care. Brincidofovir and Vaccinia Immune Globulin (VIGIV) are additional therapeutics, available from the SNS, that can be considered for treatment of mpox in certain patients who might benefit from combination therapy with tecovirimat or may require an alternative treatment to tecovirimat. Cidofovir is a commercially available antiviral that has the same mechanism of action as brincidofovir and could also be considered. For patients with eye infections involving mpox, trifluridine ophthalmic solution might also be considered after consultation with ophthalmologists.

Additional therapeutics can be considered in combination with tecovirimat or as an alternative therapy for treating MPXV infections in certain situations, such as

1. Ocular infections
2. People with protracted or life-threatening manifestations of mpox because, for example, of severe immunocompromise such as HIV CD4 cell count <200 cells/mm³ or other comparable severe immunocompromise
3. People with clinically significant disease progression while receiving tecovirimat or who have recrudescence (initial improvement followed by worsening) of disease after an initial period of improvement on tecovirimat
4. People for whom there is concern that the virus affecting the patient is resistant to tecovirimat, for example, because new mpox lesions have developed despite more than 2 weeks of tecovirimat treatment
5. People allergic to or otherwise unable to receive tecovirimat

Decisions on whether and when to use these additional or alternative therapeutics must be made individually for each person and can depend on a variety of clinical and other parameters. Healthcare providers preferring a clinical consultation with CDC or who have patient management questions may contact the CDC during regular business hours at poxvirus@cdc.gov and after hours via the CDC Emergency Operations Center [EOC] at (770) 488-7100.

Brincidofovir (also known as CMX001 or Tembexa)

Brincidofovir is a prodrug of cidofovir that is approved by the FDA [670 KB, 21 pages] for the treatment of human smallpox disease in adult and pediatric patients, including neonates. Data are not available on the effectiveness of brincidofovir in treating MPXV infection in people. However, it has shown to be effective against orthopoxviruses in in vitro and animal studies. Brincidofovir should not be used simultaneously with cidofovir.

Brincidofovir is made available from the SNS for treatment of mpox to clinicians who request and obtain an FDA-authorized single-patient emergency use IND (e-IND). FDA's brincidofovir e-IND eligibility criteria among adult and pediatric patients (including neonates) with mpox include:

• Lab-confirmed mpox
• Have severe disease OR are at high risk for progression to severeA disease,
• AND meet any of the following:
  • experience clinically significant disease progression while receiving tecovirimat or who develop recrudescence (initial improvement followed by worsening) of disease after an initial period of improvement on tecovirimat, OR
  • are otherwise ineligible or have a contraindication for oral or intravenous tecovirimat, OR
    
  • Are severely immunodeficient (e.g., uncontrolled HIV infection – CD4 < 200). Severely immunodeficient patients without prior tecovirimat use can simultaneously initiate combination therapy with brincidofovir and tecovirimat

Nearly all patients who receive brincidofovir are severely immunocompromised and receive brincidofovir concomitantly with tecovirimat and/or VIGIV. Brincidofovir should not be used simultaneously with cidofovir. Clinicians can switch patients between IV cidofovir and brincidofovir right away without a drug holiday.

Clinicians with mpox patients needing brincidofovir treatment may submit an e-IND request to FDA by email (DDI.EIND@fda.hhs.gov) or phone 301-796-3400 or 1-855-543-3784 during normal business hours (8 am-4:30 pm ET M-F). At any time, they can call the FDA Emergency Coordinator at 1-866-300-4374 or 301-796-8240 or email CDER-EIND@fda.hhs.gov and call the CDER Emergency Coordinator at 301-796-9900.

Vaccinia Immune Globulin Intravenous (VIGIV)

VIGIV is licensed by FDA [196 KB, 18 pages] for the treatment of complications due to vaccinia vaccination. However, it is not approved for treatment of mpox. Therefore, CDC holds an expanded access IND protocol [581 KB, 24 pages] that allows the use of stockpiled VIGIV for the treatment of orthopoxviruses (including MPXV) in an outbreak.

Data are not available on the effectiveness of VIGIV in treatment of MPXV infection in humans. It is unknown whether a person with severe mpox will benefit from treatment with VIGIV. However, healthcare providers may consider its use in severe cases in which the development of a robust antibody response may be impaired (i.e., if the patient is severely immunocompromised). Patients who receive VIGIV typically concomitantly receive tecovirimat and either brincidofovir or cidofovir.

VIGIV can also be considered for prophylactic use to prevent mpox in persons with MPXV exposure who are either severely immunocompromised or have a contraindication to receipt of mpox vaccination.

VIGIV is available upon clinician request to CDC on a case-by-case basis. To request VIGIV, clinicians can contact the CDC Clinical Consultation Team by email (poxvirus@cdc.gov) during business hours, or for urgent clinical situations, contact the CDC Emergency Operations Center (770-488-7100). Informed consent [293 KB, 6 pages] must be obtained prior to administration. The remaining VIGIV IND fillable forms will be provided to clinicians requesting VIGIV.

Cidofovir (also known as Vistide)

Cidofovir is an antiviral medication that is approved by the FDA for the treatment of cytomegalovirus (CMV) retinitis in patients with Acquired Immunodeficiency Syndrome (AIDS) and is commercially available in intravenous formulation. Data are not available on the effectiveness of cidofovir in treatment of MPXV infection in humans. However, there is evidence of cidofovir efficacy against orthopoxviruses in in vitro and animal studies. It is unknown whether a person with severe mpox will benefit from treatment with cidofovir, although its use may be considered in such patients. Brincidofovir (a prodrug of cidofovir) may have an improved safety profile over cidofovir. Serious renal toxicity and other adverse events observed during use of cidofovir to treat CMV infections have not been observed with brincidofovir (but brincidofovir is associated with other potential adverse events). Cidofovir should not be used simultaneously with brincidofovir. Clinicians can switch patients between IV cidofovir and brincidofovir right away without a drug holiday. Nearly all patients who receive cidofovir for mpox are severely immunocompromised and receive cidofovir concommitantly with tecovirimat and/or VIGIV.

Current CDC mpox studies

Virologic and Immunologic Characteristics of Severe Mpox in People with Advanced HIV (VIRISMAP)

People with advanced HIV who contract MPXV have an increased risk of severe manifestations of mpox and mortality from mpox. CDC published Interim Clinical Considerations for Severe Manifestations of Mpox to provide guidance for these cases. CDC is also collaborating with the National Institutes of Health to study the extent of mpox viral spread and immunologic markers in people with advanced HIV. The goal of the study is to determine why some patients experience severe mpox manifestations and to increase understanding of mpox pathogenesis. The study results may inform treatment and prevention of severe illness and deaths associated with mpox in people with advanced HIV.

The study will include U.S. residents 18 years of age or older who have HIV with CD4 counts of < 200 cells/mm³ and are hospitalized with probable or confirmed mpox. During hospitalization, clinicians will collect physical exam data and samples for further analysis.