Key Messages: 

• Update June 2024: The eligibility criteria for tecovirimat (TPOXX) treatment for patients with mpox has been revised in the Centers for Disease Control and Prevention (CDC) Expanded Access Investigational New Drug (EA-IND) protocol.
• ​The ​current version of the EA-IND protocol (PDF) is version 6.4 dated June 5, 2024. Refer to Section 2.0 of the protocol for the full list of eligibility criteria.
• The ​CDC Institutional Review Board (IRB) approved the protocol amendment on June 5, 2024 (see the approval letter (PDF)).​
• The ​process to obtain TPOXX has not changed in California. There are two routes to obtain oral TPOXX. Oral TPOXX is primarily obtained through the Study of Tecovirimat for Human Mpox Virus (STOMP) clinical trial, when patients are eligible and willing to participate. Oral TPOXX can otherwise be obtained through local and state pre-positioned supplies in California under the EA-IND Protocol, if patients are ineligible for STOMP and meet the EA-IND eligibility criteria.
  
• Intravenous (IV) TPOXX can be obtained for immediate patient use directly from the CDC by contacting the Emergency Operations Center (EOC)​, if not available locally. Contact your local health department simultaneously, as local or state supplies may be available to fill a stopgap while awaiting shipment from CDC.
  
• TPOXX use and inventory should continue to be reported weekly through the enhanced Health Partner Order Portal (HPOP) system.
  

Mpox Treatment Information for Providers

Many patients with mpox have a mild, self-limited disease and recover without medical intervention. However, the prognosis for mpox depends on multiple factors, including immune status, previous vaccination, co-morbid conditions, and initial health status. 

Supportive Care should be initiated for all patients who have mpox symptoms. This may include topical or systemic medications and/or other clinical interventions to control pain, itching, nausea and vomiting. Patients should be monitored closely to ensure resolution of illness without complications that would require further intervention. Patients with confirmed or suspected mpox should also be screened for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. The CDC has reported that approximately 40% of mpox cases had HIV or another STI in the past year (CDC). 

Antiviral Treatment with Tecovirimat (TPOXX)

There is no treatment approved specifically for mpox virus infections. TPOXX is an FDA-approved antiviral medication for the treatment of human smallpox disease in adults and children, based on animal efficacy data and safety data in adults. The use of TPOXX for the treatment of other orthopoxvirus infections, such as mpox, in investigational. Safety trials in people have found TPOXX to be safe, with only minor side effects reported. TPOXX is available in oral and intravenous (IV) formulations.

Patients who are at high risk for severe disease or who ​progress to severe mpox​ despite supportive care and pain control should be considered for prompt TPOXX treatment. Patients with mild to moderate disease can also be treated with TPOXX through a clinical trial (more information below). The decision to treat is at the clinical discretion of the health care provider. A positive lab result is not necessary to initiate treatment if there is high clinical suspicion. TPOXX may be initiated for patients with laboratory confirmed non-variola orthopoxvirus infection or suspected infection based on known exposure(s) and/or clinical manifestations of disease.

As TPOXX is not FDA-approved for use in mpox, it is only available through specific channels. The primary route for obtaining oral TPOXX is through the Study of Tecovirimat for Human Mpox Virus (STOMP) clinical trial funded by National Institute of Allergy and Infectious Disease (NIAID). TPOXX is also available in oral or IV form through the CDC-held EA-IND protocol for patients who meet eligibility criteria.

The ​EA-IND eligibility criteria for TPOXX treatment for patients with mpox has been revised in June 2024. The current version of the EA-IND protocol [494 KB, 28 pages]​ (PDF) is version 6.4 dated June 5, 2024. Refer to Section 2.0 of the protocol for the full list of eligibility criteria. The CDC Institutional Review Board (IRB) approved the protocol amendment on June 5, 2024 (see the approval letter [372 KB, 2 pages] (PDF)​).​

Providers or facilities providing or prescribing must review and comply by the CDC-held EA-IND eligibility criteria. For more information who meets eligibility criteria for treatment using TPOXX, see Tecovirimat (TPOXX) for Treatment of Mpox | CDC.

How to Obtain Tecovirimat (TPOXX) 

I. Ordering Oral TPOXX 

Health care providers are first encouraged to enroll their patients in the STOMP trial. If an alternative source of TPOXX is needed, health care providers can contact their Local Health Department (LHD) to obtain oral TPOXX through the state stockpile under the CDC EA-IND Protocol. The LHD Medical Health Operational Area Coordinator (MHOAC)​ will submit a resource request to California Department of Public Health (CDPH), and medications will be shipped to the healthcare facility. More detail regarding each of these routes for obtaining oral TPOXX is provided below. 

Option 1 (Preferred)​: The STOMP Clinical Trial: A placebo-controlled NIAID-funded clinical trial to evaluate the effectiveness of the antiviral TPOXX – is the preferred mechanism for obtaining oral TPOXX. Enrollment in the STOMP trial is critical for possible FDA approval and commercial availability of this medication. 

1. Providers are encouraged to inform patients with mpox about STOMP and to recommend they consider seeking enrollment. The trial has both randomized and open label treatment arms.
   
2. Remote enrollment is available, and all enrolled participants receive follow-up from a clinical research site.
   
3. Patients do not have to have severe disease or be at high risk of severe illness to enroll in the randomized arm of the study.
4. The patients who meet the eligibility criteria to receive TPOXX for treatment of mpox under CDC’s EA-IND protocol can also receive oral TPOXX through STOMP. They get enrolled in the open-label arm of the STOMP study, where they are guaranteed TPOXX treatment.
5. Participants can self-enroll or be referred to one of the clinical research sites through STOMP: Study of Tecovirimat for Mpox​ or by calling the “Mpox Study Hotline” at 1-855-876-9997.
   
6. Clinic friendly promotional summaries of the STOMP study for patient and providers a can be found here: CA Prevention Training Center’s STOMP Study Patient and Provider Handouts​. These have been translated in to three languages. 

Option 2 (Alternative)​: Accessing state supplies of oral TPOXX through the CDC EA-IND: The CDC holds an EA-IND protocol, which allows the use of pre-positioned TPOXX to treat mpox during an outbreak for patients who meet eligibility criteria. 

1. To obtain oral TPOXX through this route, providers can contact their LHD MHOAC who may source oral TPOXX locally or will submit a resource request to CDPH. Medications will be shipped to the healthcare facility.
2. ​Providers or facilities must review and comply by the CDC-held EA-IND eligibility criteria and must follow the CDC requirements (see below) for use under the EA-IND protocol (PDF), including submission of the required forms.
   

II. Ordering IV TPOXX

Given ​limited state supplies and the fact that the IV formulation is rarely needed, all requests for IV TPOXX for immediate patient use should be sent directly to the CDC. Note that the US Department of Health and Human Services (HHS) no longer allows state/local health departments or providers to stockpile/pre-position IV TPOXX.

IV TPOXX remains available for  use in mpox patients who meet eligibility under the CDC EA-IND protocol (PDF) and require an IV formulation (i.e. those who are unable to take oral therapy or for whom there is a concern that oral absorption may be altered). 

1. To request IV TPOXX for immediate patient use, the first line option is through the CDC. Providers should contact the CDC by calling the CDC Emergency Operations Center at 770-488-7100 (after hours), or emailing poxvirus@cdc.gov and mpxtreatment@cdph.ca.gov​ (during business hours) to reach the CDC and CDPH Clinical Consultation Teams.
   
2. ​If CDC is unable to fulfill the request within 24 hours, providers should contact their LHD MHOAC to secure IV TPOXX through state supplies as a temporary stop-gap. Please note, there was a product shelf-life extension released for IV TPOXX and facilities may still have inventory available. The lot numbers and expiration dates for remaining oral and IV TPOXX products is found on the HHS SNS Products: Vaccines and Treatment Available for Use in the Mpox Response​.

III. CDC EA-IND Protocol Requirements​

The​ EA-IND eligibility criteria for TPOXX treatment for patients with mpox was revised in June 2024. The current version of the EA-IND protocol (PDF) is version 6.4 dated June 5, 2024. Refer to Section 2.0 of the protocol for the full list of eligibility criteria. The CDC IRB approved the protocol amendment on June 5, 2024 (see the approval letter (PDF)). Clinicians, care facilities, and hospitals providing TPOXX should immediately transition to the revised protocol, including continuing the requirements of registry and form submission, found at: ​​ ​Tecovirimat (TPOXX) IND Online Registry | CDC​.

TPOXX Reporting

Whenever a patient is initiated on TPOXX, health care providers are asked to inform the LHD corresponding to the patient’s residence. This is so that: (1) treatment information can be accurately reported in the state surveillance system (CalREDIE) and (2) local medication supplies can be monitored.​

Additionally, the US Department of Health and Human Services enhanced Health Partner Order Portal (HPOP) is the new reporting system used to track IV and oral TPOXX inventory. The federal government requires TPOXX inventory reporting and providers/facilities should report their inventory through HPOP weekly and at the time of resou​​​rce requests. 

For questions on HPOP use, contact hpop.support@hhs.gov or (833) 868-6386 (5AM – 2PM PST). 

Additional Considerations on Advanced Therapeutics for Mpox 

When prescribed orally, it is critically important to educate patients to take TPOXX with fatty meals to ensure adequate gastrointestinal absorption and to maximize serum levels of the drug. Inadequate serum levels could promote resistance. ​Dosage and administration of TPOXX guidance for adults and children is provided in the CDC EA-IND protocol (PDF) on the CDC Healthcare Professionals Guidance webpage. ​

Treatment considerations in severe or prolonged disease include the following: 

• The standard TPOXX treatment course is 14 days 
• If needed, TPOXX treatment can be extended beyond the standard 14-day course on a short-term basis (e.g., an additional 3-7 day course, with close monitoring for safety and clinical response). 
• Certain patients with severe mpox or at high risk for severe mpox (patients with HIV and CD4 count <350 cell/mm³ or other severely immunocompromising conditions) should be considered for concurrent administration of other therapeutics, including cidofovir, brincidofovir, and vaccinia immune globulin IV (VIGIV). Consultation with CDC, infectious disease specialists, and other experts for any patient who may benefit from receiving multiple therapeutics is encouraged. 
• ​For immunocompromised patients, make all efforts to minimize immune suppression to the extent possible (e.g., ensure persons with HIV are receiving effective antiretroviral therapy) and limit the use of immunosuppressive therapies (e.g., chemotherapy, TNF inhibitors), if feasible. 

Additional medical countermeasures currently available from the Strategic National Stockpile (SNS) as options for the treatment of mpox include brincidofovir, and vaccinia immune globulin. Cidofovir is also available commercially. These additional antivirals are typically used in conjunction with TPOXX for severe or refractory cases. 

The CDC has published an MMWR on Treatment Considerations for Severe Manifestations of Mpox, in addition to a previously published Health Alert Network (HAN)​ update containing recommendations for managing mpox in patients requiring additional therapeutics.

Considerations for TPOXX​ Resistance and Testing 

Clinicians should be aware of the concern for development of TPOXX resistance, especially in patients who are immunocompromised or have severe disease and require prolonged TPOXX treatment. 

CDC scientists are actively monitoring for changes in the mpox virus that could make the virus less susceptible to TPOXX. Because of the potential for the virus to become resistant to TPOXX, it is important the drug be used in a judicious manner. ​More information about tecovirimat resistance can be found below, and on the FDA and the CDC websites. 

TPOXX resistance testing considerations: 

• ​​In patients with persistent or progressive mpox after completing 14 days of tecovirimat, consider testing lesion swab samples (PDF) for possible resistance to tecovirimat and performing plasma pharmacokinetics​​​ (PDF), for public health surveillance purposes. 
• Ideally, resistance and pharmacokinetic testing should be performed concurrently to determine if any cases of confirmed resistance are associated with drug levels below target concentrations. 
  
• Collection ​of lesion samp​​​les for the purpose of whole genome sequencing with testing for resistance-associated mutations will help monitor for the potential emergence of antiviral resistance. However, individual patient results cannot be made available for directly informing individual patient treatment decisions at this time.
  

Please contact your LHD, CDPH, and the CDC with any concerns about tecovirimat resistance, or to discuss cases requiring prolonged TPOXX courses (greater than 14 days), and/or being considered for advanced therapeutics.​