Predictably, patients in underserved rural, urban communities will face challenges gaining access to approved study sites.
At press time, there were more than 18,000 reported cases of monkeypox in the United States and approximately 50,000 cases worldwide.1 Most US cases have been among bisexual, gay, and other men who have sex with men, which has raised concerns about marginalizing high-risk communities, stigmatizing this population, and falsely minimizing the risk to other groups. There are concerns of repeating errors that occurred in the early phases of the HIV epidemic when inadequate attention was paid to the public health risks because of similar marginalization of high-risk groups and an inadequate, slow response. Anyone can be infected with the monkeypox virus through close personal contact with an infected individual, so it must be treated as a public health concern for all.
In a guest essay published in the New York Times, Scott Gottlieb, MD, former FDA commissioner and a senior fellow at the American Enterprise Institute, warned that monkeypox is at risk of becoming the next national public health failure because of a lack of national infrastructure, inadequate testing capacity, and limited stockpiles of effective treatments and vaccines. Overall, there is the risk of failing to heed the lesson learned from prior outbreaks such as COVID-19 and HIV, he wrote.2
In response to concerns and criticism about an inadequate response, the Biden administration declared monkeypox a national health emergency on August 4, 2022, which will result in greater resources being directed toward the public health management of this outbreak.
There are several significant differences from prior major outbreaks in that monkeypox is generally a self-limited process that is only rarely fatal and is primarily managed on an outpatient basis. Although self-limited, monkeypox can present with severe symptoms, including painful esophagitis and proctitis, necessitating hospitalization for adequate management. Unlike other recent viral outbreaks, there are FDA-approved treatments and vaccines for orthopoxvirus infections that have good cross-coverage for monkeypox. Unfortunately, the strategic reserves for these agents were primarily intended to manage a bioterrorism event involving smallpox and were woefully inadequate in supply to respond to the demand created by this outbreak. This has led to many concerns about the supply of vaccine for pre- and post-exposure prophylaxis for most high-risk individuals and criticism of how the vaccine is being distributed from an equity perspective.3
The federal government has taken steps to increase the supply of the JYNNEOS vaccine and has authorized the use of the intradermal administration that increases the number of doses available 5-fold because of a much lower dose requirement, though evidence of effectiveness of the low-dose intradermal vaccine is very limited. Despite not being FDA approved for monkeypox, the JYNNEOS vaccine is being made broadly available through public health departments and other providers, which is much different than how the FDA-approved antiviral tecovirimat (TPOXX) is being managed.
TPOXX is FDA approved for the treatment of smallpox in adults and children. There is limited clinical evidence that it can shorten the course and severity of other orthopoxvirus-associated infections, including monkeypox. Overall, the drug is safe, with a relatively benign adverse effect profile, and it is available as both an injectable product and an oral capsule. Treatment with TPOXX is recommended as a medical countermeasure in select patients with severe monkeypox, for individuals who are at elevated risk for developing a severe presentation, and for patients with aberrant monkeypox infections.4
TPOXX is only available through a CDC-managed expanded access protocol, sometimes referred to as a treatment investigational new drug (IND) protocol. This can be done using an emergent single-patient IND application with retroactive institutional review board (IRB) approval, or it can be approved in advance by an IRB as a multipatient expanded access protocol. This requires the investigating physician(s) to complete an FDA 1572, revise a consent form template for the site, obtain IRB approval, obtain informed consent from each patient, fill out case report forms that have been simplified in recent weeks, and manage the receipt and distribution of the drug following good clinical practice (GCP) standards. The drug distribution to clinic sites is then managed by individual jurisdictions, such as state health departments. This level of complexity is beyond the experience and capabilities of many clinicians who may be involved in the management of these patients, and therefore a patient will need to be referred to a provider listed on the FDA 1572 for a site with an approved expanded access protocol, representing a major barrier to treatment access and an elevated risk of inequity.
It is predictable that patients in underserved rural and urban communities will face challenges gaining access to approved study sites and therefore access to treatment. The drug being managed as “experimental” may also create distrust in underserved communities. It would greatly simplify the process to make the drug available to be prescribed off-label by any qualified physician, which is done every day for many other approved drugs, including the FDA-approved orthopoxvirus vaccines. Although there would be a loss of data collection, that should be offset by much greater and more equitable access to treatment during this declared public health emergency.
This is also a call to action for health system pharmacists, many of whom are familiar with the treatment IND protocol process and can facilitate the regulatory filing process for busy frontline physicians. The pharmacy can also bring the expertise needed for proper handling of investigational drugs under GCP standards and facilitate the timely completion of case report forms. In addition, the pharmacy could distribute the drug widely using overnight couriers for patients with more limited access to large health systems most often qualified to manage treatment IND protocols. Initial and follow-up patient visits can be completed using telehealth technology where available, and then the drug can be distributed from the pharmacy.
Working closely with other members of the patient care team, pharmacists experienced in clinical research processes can take the lead in assuring equitable access to treatment options for monkeypox.
ABOUT THE EDITOR
Curtis E. Haas, PharmD, FCCP, is director of pharmacy for the University of Rochester Medical Center in New York.
1. Monkeypox: 2022 outbreak cases and data. CDC. Updated August 22, 2022. Accessed August 30, 2022. https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html
2. Gottlieb S. Monkeypox is about to become the next public health failure. New York Times. July 30, 2022. Accessed August 30, 2022. https://www.nytimes.com/2022/07/30/opinion/monkeypoxpublic-health-failure.html.
3. Fewer Black people receiving monkeypox vaccine doses compared to the general public, CDC says. PBS Newshour. August 26, 2022. Accessed August 30, 2022. https://www.pbs.org/newshour/health/black-people-receiving-less-monkeypox-vaccine-compared-to-general-public-cdc
4. Monkeypox: treatment information for healthcare professionals. CDC. Updated July 28, 2022. Accessed August 30, 2022. https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html.