As the world continues to grapple with public health challenges, the recent monkeypox outbreak has drawn significant attention. With its origins dating back to 1958, monkeypox is not new, but the recent global surge in cases highlights the need for effective treatments and preventive measures.
Understanding Monkeypox: A Re-emerging Threat
Despite the name, monkeypox has little to do with monkeys. It is a zoonotic virus, meaning it spreads from animals to humans, but the exact animal reservoir remains unknown. Traditionally endemic to parts of Africa, monkeypox typically presents with symptoms such as fever, swollen lymph nodes, and a characteristic rash potentially developing into painful pustules.
A notable feature of this virus is its connection to smallpox, which was eradicated in 1980. Because of this relationship, many treatments and vaccines developed for smallpox may also be effective against monkeypox. The U.S. government, for example, has invested in treatments like Tecovirimat (TPOXX), initially designed to combat smallpox but now being repurposed for monkeypox.
Therapeutic Landscape: Vaccines and Treatments
Prevention remains a crucial focus in controlling the monkeypox outbreak. Two vaccines developed for smallpox prevention, JYNNEOS and ACAM2000, are currently used to protect against monkeypox. Of these, JYNNEOS is the primary vaccine used in the U.S., administered in two doses four weeks apart. While there is optimism about its protective benefits, the lack of human efficacy data leaves some uncertainty about its effectiveness in preventing monkeypox infection.
As for treatment, four therapies are being considered:
- Tecovirimat
- Cidofovir
- Brincidofovir
- Vaccinia Immune Globulin
Among these, Tecovirimat stands out as the most promising option due to its ability to specifically target the virus’s life cycle. Although it has shown efficacy in animal models, more clinical data is needed to confirm its effectiveness in humans. Other treatments, such as Cidofovir and Brincidofovir, come with significant risks, including kidney and liver toxicity, making them less favorable options for widespread use.
Ongoing Research: The STOMP Trial
One of the most important developments in the fight against monkeypox is the National Institutes of Health (NIH)-funded clinical trial known as the STOMP trial: Study of Tecovirimat for Human Monkeypox Virus. Led by Dr. Tim Wilkin and his team at Weill Cornell Medicine, this trial is designed to assess the efficacy of Tecovirimat in treating monkeypox.
The study features three arms: a blinded arm with Tecovirimat versus a placebo, an open-label arm for individuals with severe disease, and a dosing arm for vulnerable populations such as children and pregnant women. This design allows for an ethical balance between obtaining essential efficacy data while ensuring those at highest risk still receive treatment. Patients who develop severe symptoms during the trial are withdrawn from the blinded group and given open-label Tecovirimat, ensuring no participant endures unnecessary suffering for the sake of research.
Ethical Considerations in Clinical Trials
Conducting clinical trials during an outbreak raises unique ethical challenges. One of the primary concerns is whether it is ethical to use a placebo when there are promising treatments available, even if those treatments have not yet been fully proven. In the case of the STOMP trial, the investigators recognized the ethical tension between providing immediate access to a potentially effective drug and the need to collect controlled efficacy data.
By offering open-label Tecovirimat to those with severe disease or at high risk of complications, the study design addresses this tension. This allows researchers to gather critical data while ensuring the patients with the most pressing needs are not left untreated. The ethical balance struck in this study design could serve as a model for future clinical trials during public health crises.
Lessons Learned from COVID-19
The speed and efficiency with which the STOMP trial was launched can be attributed, in part, to lessons learned from the COVID-19 pandemic. The global response to COVID-19 has fundamentally changed the landscape of clinical research. Protocols developed to streamline research during the pandemic, such as remote consenting and video visits, have carried over into monkeypox research. Additionally, the pandemic highlighted the importance of rapid data collection and transparency, ensuring trials like STOMP are conducted with urgency.
One of the most significant takeaways from the COVID-19 response is the potential for accelerated drug and vaccine approval processes. The success of the COVID-19 vaccines has raised public expectations for fast, effective responses to health emergencies. While it is unlikely all future trials will progress at the same pace as COVID-19 vaccine trials, the pandemic has shown streamlined processes are possible without compromising safety and efficacy.
Looking Ahead
As monkeypox continues to spread globally, the urgency for effective treatments and vaccines grows. The STOMP trial is a crucial step toward understanding how to best treat and prevent monkeypox in diverse populations. While challenges remain – particularly in gathering sufficient data during a rapidly evolving outbreak – the dedication of the research community offers hope for timely solutions.
Clinical research, particularly in infectious diseases, has never been more important. With the lessons learned from COVID-19 and ongoing innovations in trial design, there is optimism that monkeypox can be brought under control. For now, continued vigilance, ethical research practices, and public health preparedness are key to managing this emerging threat.
