SIGA Technologies' Trial Results Benefits Mpox Treatment Despite Not Meeting Primary Endpoint
The impact of including patients with advanced disease and the role of comprehensive care in the PALM 007 clinical trial, which evaluated the antiviral tecovirimat for treating monkeypox in the Democratic Republic of the Congo.
Early this morning, SIGA Technologies announced the results of the PALM 007 clinical trial, which assessed antiviral tecovirimat for treating monkeypox (mpox) in the Democratic Republic of the Congo (DRC) did not achieve its primary objective of showing a statistically significant improvement in lesion resolution compared to a placebo. Regardless, tecovirimat's safety profile was consistent with the placebo's and aligned with previous studies' findings.
Jay Varma, MD, Chief Medical Officer at SIGA Technologies, discussed findings from the trial with Contagion. He acknowledged that although the primary goal was not met, he explained that the trial showed benefits in patients treated early or those with severe disease. Varma elaborated on a few reasons supporting this:
“Firstly, regarding early treatment, this study was designed with certain humanitarian considerations in mind. Instead of targeting the study solely towards those most likely to show a benefit from the drug, it included patients who could present much later in the course of their illness. For example, about 20 to 30% of patients presented more than seven days after the rash began. This significantly diluted the impact of the study findings. So, including patients who were unlikely to benefit much was a major reason why the primary endpoint wasn’t met,” Varma said.
Varma compared tecovirimat to other antivirals for infections like flu or COVID-19, noting that these drugs don’t kill viruses but prevent them from spreading through the body. He continued with his second point about patient benefits:
“The study was initially designed based on historical data about how quickly lesions resolve, under routine conditions. In this study, all patients were hospitalized, provided with food, nutrition, and treatment for other illnesses. This comprehensive care improved their outcomes by about 25 to 50%, with patients resolving their illnesses approximately two days faster than historically. This created a challenge in demonstrating a benefit in patients who might have had milder disease, which is why the treatment benefit was mainly observed in patients with severe disease or those treated early.”
Varma made an analogy of how regulatory agencies and clinical or public health agencies evaluate a drug. “Regulatory agencies, like referees in a sports game, focus on rule adherence. In contrast, doctors and public health agencies consider the broader performance and value. When evaluating the total data, it’s clear that the drug has value, particularly for patients treated early or those with severe disease.”
Regarding the new mpox strain, clade I, Varma commented on its transmission modes. “Everything we know about the mpox strain circulating in the DRC, known as clade I, shows it’s still quite similar to the clade 2 strain spreading elsewhere. We don’t think respiratory transmission is a major factor at present, viruses evolve, and anything is possible, but respiratory transmission isn’t considered a primary driver right now,” Varma said. “The main difference between the two clades is the severity of illness. Clade I generally causes more severe disease compared to clade II, which can be less severe or occur in people with advanced AIDS or other immune suppression. Smallpox, a related virus, represents the most severe end of this continuum.”
Future Directions
Future research is ongoing with trials such as STOMP, UNITY, Platinum-CAN, and EPOXI to assess tecovirimat’s efficacy under various conditions. It’s essential to use lessons from this trial to improve these ongoing studies. Varma highlighted key factors for future research:
“It's crucial for patients and observers to understand that this study isn't the final word on the drug or on mpox. Based on everything we know about the drug’s biology and safety, it’s important to study it further for the endpoints mentioned, and also in different patient populations.”
It's important to note the differences in affected populations: in the DRC, most diagnoses are among children, usually without HIV, who likely contracted the infection through close skin-to-skin contact or possibly from animals. In contrast, in the US and Europe, the affected population is primarily adult men who are gay, bisexual or have other sexual partners, with many also living with HIV.
“Lesions often present differently, with more in the genital or anal areas and they tend to be extremely painful. Therefore, future research should also focus on patient-centered endpoints, like pain and discomfort relief, as observational data from compassionate use indicates that pain and discomfort resolve faster with the drug.”
SIGA Technologies and NIAID are analyzing these studies to better understand the benefits of tecovirimat. Together, these trials aim to deepen knowledge of tecovirimat and refine its application for managing mpox.
“SIGA is taking is partnering with governments worldwide and large multilateral organizations like WHO to ensure the drug is available for two main purposes. First, to support research and ensure high-quality data to confirm the drug’s effectiveness and target population. Second, to provide the drug for compassionate use, especially for those with severe disease or advanced immune suppression. We want to make sure it’s available while critical data is being collected.”
