The study is unusual in that it is based on a two-part human challenge trial, where researchers purposefully infect people with a pathogen to test a new therapy. Challenge studies speed up research because scientists don’t have to wait for their study participants to get sick out in the real world. They can also enroll fewer people, knowing that participants will inevitably catch a germ. But they’re also risky and only considered ethical when the need for a new treatment or therapy is thought to outweigh the potential risks to study participants.
RSV causes cold-like symptoms for millions of adults and children in the US each year. In severe cases, the infection can spread to the lower lungs, leading to pneumonia and inflammation of the smaller airways deep in the lungs. Young children can struggle to clear the copious mucus the infection produces, and about 58,000 children are hospitalized annually.
“All of us pediatricians start dreading RSV, from November to March. We know we’re just going to get inundated with it,” said Dr. Jill Foster, a pediatric infectious disease specialist at the University of Minnesota.
Covid-19 has upended RSV season for the past two years. It’s normally a winter virus, but in 2020, RSV all but disappeared as people stayed home and wore masks. The virus roared back early in 2021, however, fueled by the lifting of restrictions in many parts of the country.
At the same time, doctors don’t have great options to prevent or treat the disease. They can prescribe an injected and expensive monoclonal antibody that’s given every three months to prevent RSV in children who may be especially vulnerable to its effects, such as those who are immunocompromised. There’s an inhaled drug called ribavirin that’s only modestly effective and can have serious side effects, so it’s only given in the hospital to the sickest children. Scientists have yet to develop a safe or effective vaccine against it.
Drug reduced symptoms, but more tests need to be done
For the challenge trials, researchers used a milder strain of RSV, called Memphis 37, that’s been shown to resolve on its own in humans after about two weeks.
“It’s all very well controlled,” said Alaa Ahmad, who led the study for Enanta Pharmaceuticals, the company developing the drug.
The new drug, known as EDP-938, works by preventing the virus from making copies of itself in the body. It can be given as a liquid or a pill.
The study enrolled healthy adults between the ages of 18 and 55, who had very low levels of antibodies against the RSV virus in their blood — probably left over from previous infections. They were experimentally infected with the Memphis 37 strain of the virus, then placed in a quarantine unit for 12 days, until they tested negative. There were 115 people in the first part of the study and 63 people in the second.
Researchers then took nasal swabs until they detected a brewing infection, then started one of two doses of the medication or a placebo.
Side effects were mostly mild. People on the drug were more likely to experience headaches, dizziness and diarrhea compared to those who were taking a placebo.
At all doses, viral levels were significantly lower in people taking the drug compared to those who got a placebo. Those on the drug had fewer symptoms too. They made about 70% less mucus than people in the placebo group.
Foster, who reviewed the study but wasn’t involved in the research, says the new drug looks promising, but she has questions, such as: “Will it work in in infants with RSV?”
Because babies have such small airways, they’re the group at highest risk from an RSV infection. But it’s hard to test new drugs in infants, because institutional review boards, the groups that greenlight clinical trials, don’t usually allow researchers to use them in experiments.
Foster also wants to know if it will work in the real world.
Antiviral drugs tend to work best when taken early in an infection. In the challenge trial, there was no guesswork involved in when to give the drug since scientists were closely monitoring people for signs of infection.
Out in the real world, people may be slow to pick up on their symptoms and get a test too late to benefit.
There’s some evidence that children who get RSV infections may be more likely to develop asthma later in life.
From that standpoint, Foster says she could see this new drug making a big difference if children who were treated with it were less likely to develop asthma down the road.
“That would be a total game changer, is if you could treat RSV early and it would make a difference, later, development of asthma. Hopefully, that’s something that they will look at,” she said.
Enanta says that based on these promising early results it has already started the next phase of its clinical testing for EDP-938. In these studies, they’re testing the drug on people who catch the virus on their own. Because the US had such a bad RSV season last year, they said they’re nearly finished with that one and will share results within the next three months.