Three Massachusetts hospitals have received approval to launch the first US clinical trial of a Japanese flu drug that could be used to treat COVID-19, according to a doctor involved in the effort.
The trial — which will take place at Massachusetts General Hospital, Brigham and Women’s Hospital, and UMass Memorial Medical Center in Worcester — was approved by the federal Food and Drug Administration Tuesday. The small, randomized trial of the antiviral drug favipiravir will look to study its effectiveness as a treatment for patients infected with the coronavirus, according to doctors involved in the study.
The Japanese government has touted the drug, known by the brand name Avigan, as a possible treatment for COVID-19 Medical authorities in China have called the drug “clearly effective” in treating coronavirus patients after conducting two clinical trials.
The trial is the latest development in the global race to find effective drugs to treat the potentially deadly illness. It is one of several efforts underway here in Boston and around the world among biopharmaceutical companies and hospitals seeking to deliver new weapons to health care providers battling the virus sweeping the globe.
One key focus of that supercharged research effort has involved looking at existing antiviral medicines to see if they prove effective against the coronavirus. The task is all the more urgent given most experts say a vaccine is at least a year away from FDA approval.
The initial US trial, as planned by the Massachusetts researchers, would involve roughly 50 or 60 patients across the three sites. One group would receive the drug along with the normal standard of care, while a second control group would receive only the normal care COVID-19 patients currently receive, according to officials involved in the trial. Further details about the protocol were not immediately available.
Dr. Keith T. Flaherty, who is leading a team of experts at MGH reviewing all the possible coronavirus-related clinical trials to see if the hospital should participate, said his group has so far deliberated over 30 possible trials since launching.
“We have to prioritize, and this absolutely rose to the top,” he said of the favipiravir trial, calling it one of the highest-priority studies the renowned teaching hospital is undertaking.
While the initial trial is relatively small, Flaherty said the hope is the hospitals could expand it if the drug shows promise.
The drug was produced by a pharmaceutical subsidiary of Japan-based Fujifilm more than a decade ago as a treatment for new and reemerging strains of influenza. The company has not yet confirmed the details of the US trial.
Some virologists and regulators have raised concerns about using it as a coronavirus treatment without further testing, though the Trump administration is reportedly pushing the FDA to approve it as an emergency treatment for the virus, according to Politico.
Doctors involved in the planned Massachusetts trial note that the drug has been used widely in humans, so the side effects are relatively well known. The potential benefits for a COVID-19 patient ill enough to be admitted to the hospital far outweigh the potential risks of side effects, the doctors said.
But they said it is important to conduct proper randomized trials on this and other potential treatments so researchers can gather evidence on which drugs actually improve patient outcomes.
“The drug looks promising,” said Dr. Robert W. Finberg, an infectious disease specialist at UMass Memorial, who is the principal investigator on the trial at that hospital. He has done previous studies on favipiravir as a treatment for influenza, and has an existing relationship with the drug maker that led to the collaboration for the US coronavirus trial.
The drug works by causing the virus to misread its genetic instructions and not reproduce correctly, “so that the virus eventually melts down in the test tube,” Finberg said, describing his previous research on it. Researchers believe it will work the same way with the coronavirus, he said.
“It’s actually a very safe drug," Finberg said.
He said researchers would not want to give it to pregnant women, however, because there is evidence it could cause birth defects.
Cell culture tests indicate the drug does show some evidence of activity against the coronavirus in a test tube, he said, which is among the reasons researchers are encouraged.
“These things do take a little bit of time," Finberg said of human trials of the drug’s efficacy. "We will not get an instant answer.”
Chinese researchers carried out two clinical trials of favipiravir, reporting positive results, though Fujifilm Toyoma Chemical, the drug’s developer, has declined to comment on the Chinese claims. Some of the data out of China showed that patients who were given the medicine were virus-free more quickly than those who did not receive the drug, and X-rays showed lung improvement among more of those who took the drug, according to news reports.
Doctors in Japan are conducting their own clinical trials of the drug for the treatment of COVID-19 in patients with mild to moderate symptoms.
Favipiravir is similar to another antiviral drug undergoing clinical trials as a coronavirus treatment, the experimental drug remdesivir. Both MGH and Brigham are conducting separate trials on remdesivir, which also targets the way the virus replicates itself and spreads within an organism. UMass Memorial is also studying remdesivir, according to Finberg.
Having trials on both drugs will help researchers determine “which of these two now merits being a backbone that we build on,” said MGH’s Flaherty. He said similar investigations are happening on another track looking for an existing anti-inflammatory drug that can help tamp down the “overly exuberant” immune response that the virus triggers in some patients, causing potentially lethal results. The expectation is that patients would need to be treated with both types of drugs, he said.
Any promise in treating symptoms is welcome news, said Dr. Rochelle Walensky, MGH’s chief of infectious diseases, though longer-term studies will be needed to show whether any of these drugs can help prevent patient death.
“It’s a really tough time as an infectious disease doc. For the last 20 years there haven’t been many diseases where we don’t have anything on the shelf to even try. We are really motivated to understand how drugs might be helpful and work,” she said. “It’s crushing to be on the front lines to see people getting worse in front of you and have nothing to offer.”