A day after the World Health Organization again declared mpox a public health emergency, more bad news came out about the virus.
On Thursday, the National Institutes of Health said that SIGA Technologies’ antiviral tecovirimat did not significantly reduce the duration of mpox lesions in a randomized clinical trial of children and adults with the endemic clade I version of the virus in the Democratic Republic of the Congo.
The virus has been spreading to multiple countries in Africa this year. The Africa Centres for Disease Control and Prevention said Tuesday there have been more than 17,000 suspected cases and more than 500 deaths on the continent so far this year. Africa’s CDC declared mpox a public health emergency of continental security a day before the WHO’s alarm.
The PALM 007 trial launched in October 2022 and included 597 people at two sites in the DRC. They were hospitalized for at least 14 days and had laboratory-confirmed mpox. The NIH said the antiviral was well-tolerated and participants had no drug-related serious adverse events.
Jeanne Marrazzo“These findings are disappointing, but they give us essential information and reinforce the need to identify other therapeutic candidates for mpox while we continue research on tecovirimat use in other populations with mpox,” NIAID Director Jeanne Marrazzo said in a press release.
In a statement, SIGA said the trial was a “controlled environment” and that study participants received “a level of care unavailable to most mpox patients in real world situations.” It said the impact of those factors on the trial results “is not yet known.” SIGA’s stock price $SIGA was down about 29% in Thursday afternoon trading.
“These data showing maximum benefit in patients treated early and with severe disease are entirely consistent with the mechanism of action of tecovirimat and with the studies in animals that led to U.S. FDA approval of this medicine for smallpox, a virus closely related to monkeypox virus, but which produces much more severe illness,” SIGA chief scientific officer Dennis Hruby said in a statement.
Dennis Hruby“We believe these data warrant further investigation and support our view that post-exposure prophylaxis will be vital for treatment of severe cases of mpox and all cases of smallpox,” he added.
The US CDC opened up tecovirimat, also known as Tpoxx, to an expanded access program when mpox spread stateside in the summer of 2022. The antiviral is approved by the FDA for smallpox and has been in a strategic national stockpile. It’s approved for mpox and other orthopoxviruses in the EU, Norway and the UK.
There are a few approved vaccines for the virus, including Bavarian Nordic’s Jynneos. Africa CDC Director-General Jean Kaseya has said the shots are expensive, according to a Bloomberg report. Covid-19 vaccine makers Moderna and BioNTech are testing new shots for mpox as well. BioNTech’s Phase 1/2 trial is slated to have a primary completion in October, and Moderna’s Phase 1/2 study is expected to wrap up next June, according to a federal trial database.
Need for efficacy data
“We currently lack efficacy data that would help us understand how well this drug may mitigate painful monkeypox symptoms and prevent serious outcomes,” then-NIAID Director Anthony Fauci said in a September 2022 statement.
At that time, NIAID and the AIDS Clinical Trials Group started STOMP, a Phase 3 trial of the antiviral, to get a better sense of tecovirimat’s efficacy and potentially support a label expansion. The study is being conducted in the US, Argentina, Brazil, Japan, Mexico, Peru, Puerto Rico, South Africa and Thailand. It is expected to finish next summer, according to a federal trial registry.
Timothy Wilkin“It’s not acceptable to provide ineffective drugs to thousands of people. In addition, we need an effective therapy both for the current strain of the epidemic but also for areas of the world where it’s endemic and there’s a high mortality rate and a public health issue that needs to be addressed,” Timothy Wilkin, protocol chair of STOMP, told Endpoints News in a September 2022 interview.
“We’ve learned many times over the years that infectious disease problems in other parts of the world can affect us in the US, and we are safer in the US if we help to solve these problems before they become problems in the US,” Wilkin continued.
In an interview on Thursday, Wilkin said the STOMP study is about 60% enrolled and could be fully enrolled in seven to nine months.
In addition to STOMP, three other randomized trials are testing tecovirimat: UNITY, Platinum-CAN and EPOXI.
SIGA chief medical officer Jay Varma, who has been an advisor to the CDC, Africa CDC and New York City, said the company hopes more trials will show the drug works when given early in the course of disease or to those with severe cases.
“The second thing that we’re interested in seeing are other endpoints that are very relevant to patients,” he said. “The endpoint that was chosen for this trial [PALM 007] is the complete resolution of your rash, and while that is certainly important for everybody who’s infected, people also may care a lot about pain and discomfort. We know that in the US, for example, during the 2022 outbreak, the main reason that patients were hospitalized was actually for pain control.”
Jay VarmaVarma said a protocol has been developed for a multi-country study in Africa, but that was put on hold to wait for Thursday’s results.
“We are in ongoing discussions with a number of different people about looking at ways to ensure that we can study this drug specifically with an endpoint in mind of early treatment or treatment of severe disease so that we can get the best quality data that’s needed for public health decision-making,” he added.
The first human case of mpox was identified in 1970. Clade I, the virus studied in the trial, is endemic in Central Africa and can lead to severe illness. A milder version, Clade II, is what made international headlines in 2022.
Ayisha Sharma contributed reporting.
Editor’s note: This story was updated to include information from interviews with Jay Varma and Timothy Wilkin.