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 have intact immune systems and don't have a skin disease, supportive care and pain control will help them recover without medical treatment.

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, a severe manifestation of mpox that 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.

Data from one study was released in August 2024, but more information is needed to determine tecovirimat's effectiveness in treating mpox infection in people. Based on the animal efficacy data that showed survival benefit over placebo in lethal animal models, it may be reasonable to anticipate tecovirimat may provide benefit in treating some people with disease caused by orthopoxviruses, including the virus that causes mpox. However, whether and how the efficacy in animals may translate to humans with active disease, the patients who might benefit from tecovirimat, and what specific clinical benefits might occur with tecovirimat are unknown currently.

In September 2024, a summary of data was published in New England Journal of Medicine (NEJM) Evidence describing more than 7,100 patients who were prescribed tecovirimat under the EA-IND protocol. While EA-IND data provide descriptive data on treated patients, ongoing clinical trials are essential to determine the efficacy and safety of tecovirimat in people with mpox.

Tecovirimat for treatment of mpox may be obtained through one of two channels:

Study of Tecovirimat for Mpox (STOMP) Trial

The National Institute of Allergy and Infectious Disease is conducting the Study of Tecovirimat for Mpox (STOMP) clinical trial to assess the efficacy of tecovirimat. STOMP has an open-label TPOXX arm for patients who are severely immunocompromised, have certain active skin conditions or severe disease, for pregnant or lactating people and children under 18 years of age. All patients in this arm of the trial will receive oral TPOXX.

Non-pregnant or non-breastfeeding adults who have mild illness and are not at high risk of developing severe illness (e.g., without severely weakened immune system or certain active skin conditions such as eczema) can only get oral TPOXX by enrolling in STOMP's randomized arm. Two-thirds of participants in the randomized arm will receive TPOXX.

Data from this trial will help scientists learn which patients get the most benefit from this therapeutic and guide regulators who decide whether to approve its use for mpox. Patients should be informed about STOMP and encouraged to consider enrollment.

Expanded Access-Investigational New Drug (IND) Protocol

CDC holds an Expanded Access-Investigational New Drug (EA-IND) protocol that allows for the use of stockpiled tecovirimat to treat patients with mpox who meet EA-IND eligibility criteria. Tecovirimat is available orally or intravenously for certain patients with (or who are at high risk for) protracted or life-threatening illness, including severely immunocompromised patients, people with atopic dermatitis and other conditions affecting skin integrity, children and pregnant or breastfeeding adults.

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

In October 2022, the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health, and the Democratic Republic of the Congo (DRC)'s National Institute for Biomedical Research launched the PALM007 trial 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.

There are additional studies to determine efficacy in progress. The STOMP Trial is looking at potential tecovirimat benefits to patients who have clade II MPOX and are immunocompromised or at higher risk of developing severe disease. Please continue to inform your mpox patients about the STOMP Trial and recommend they consider enrolling. To enroll in STOMP, call 1-855-876-9997. As more data become available, CDC will update TPOXX recommendations.

Additional therapeutics

Tecovirimat is typically the first therapeutic that should be considered if patients with mpox require more than supportive care. Brincidofovir and Vaccinia Immune Globulin (VIGIV) are additional therapeutics, available from the Strategic National Stockpile (SNS), that can be considered for treatment of mpox in certain patients who necessitate an additional or 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 criteria for brincidofovir e-IND treatment of human mpox disease is for adults and pediatric patients (including neonates) with positive results from human MPXV viral testing who:

• Have severeA 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 enrolled in the open-label treatment arm (Arm C) of the STOMP trial, 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 (Note: For these cases, FDA will encourage STOMP enrollment and provide link to trial information: https://www.stomptpoxx.org)

Nearly all patients who receive brincidofovir are severely immunocompromised and require brincidofovir in combination with tecovirimat. 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 mpox) in an outbreak.

Data are not available on the effectiveness of VIGIV in treatment of MPXV infection in people. Use of VIGIV has no proven benefit in the treatment of mpox and it is unknown whether a person with severe mpox infection 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.

VIGIV can be considered for prophylactic use in an exposed person with severe immunodeficiency in T-cell function for which smallpox or mpox vaccination following exposure to MPXV is contraindicated. Patients who receive VIGIV typically are concomitantly receiving both tecovirimat and either brincidofovir or cidofovir.

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 [ 828 KB, 6 pages] for the treatment of cytomegalovirus (CMV) retinitis in patients with Acquired Immunodeficiency Syndrome (AIDS), and is commercially available as an injection. Data are not available on the effectiveness of cidofovir in treatment of MPXV infection in people. However, it has shown to be effective against orthopoxviruses in in vitro and animal studies. It is unknown whether a person with severe mpox infection will benefit from treatment with cidofovir, although its use may be considered in such instances. Brincidofovir (a prodrug of cidofovir) may have an improved safety profile over cidofovir. Serious renal toxicity or other adverse events have not been observed during treatment of cytomegalovirus infections with brincidofovir as compared to treatment using cidofovir. 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 require cidofovir in combination with tecovirimat.

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.