Scientists at University of California, San Diego, have developed a way to put remdesivir and other intravenous COVID-19 treatments into a capsule that patients could safely take orally at home, according to a paper in an online issue of Antimicrobial Agents and Chemotherapy.
Since the pandemic began, scientists worldwide have been seeking a treatment that people infected with COVID-19 can take before they are so severely ill that they have to go to a hospital, and the need for it remains pressing as many people are opting not to get the vaccine and are falling ill with variants of the respiratory illness.
“The vaccines from Pfizer and from Moderna, they do a really good job of preventing people from getting ill and being in the hospital,” said Dr. Robert T. Schooley, a professor of medicine at UC San Diego School of Medicine. “But once you start having symptoms, the vaccines don’t have any effect on the course of the disease, and people can get really quite ill in this situation as the virus picks up steam. At that point, a vaccine won’t help you. Something that directly keeps the virus from growing like an antiviral drug is what you need at that point.”
Schooley, a co-author on the UC San Diego paper, said he and other researchers at UC San Diego read studies showing that remdesivir measurably reduced recovery times for hospitalized COVID-19 patients and they wanted patients to get the drug during a window of time before infections became severe and life-threatening.
To do so, Schooley said, his team had to figure out a way to keep the drug from going to organs where it does little good or to the liver, where it has proven to be toxic. Remdesivir is most effective in lung cells, Schooley said, so it’s much like real estate where “location, location, location” is a key factor in success.
Dr. Karl Hostetler, also a UC San Diego professor of medicine, had been working on so-called polymerase inhibitors like remdesivir for the last 30 years, Schooley said, and over that time, he learned that you can attach these drugs to chains of fatty acids, or lipids, and fool the gastrointestinal tract into thinking they’re pieces of sticky butter that should be absorbed.
Key elements of the remdesivir will remain intact and bioactive, traveling from the lymphatic system into the lungs, Schooley said, and as enzymes process it, the active elements of the drug are released into the lungs.
“COVID-19 is a two-stage disease,” Schooley said. “Rapid viral growth occurs shortly after infection and can trigger a misdirected immune response that results in an ‘inflammatory’ pneumonia in those who don’t do well. In order to be maximally effective, antiviral therapy must be given early in the illness before the inflammatory phase of the illness results in hospitalization.
“These compounds are designed to be taken orally, rapidly absorbed from the gastrointestinal tract and to largely bypass the liver where most of remdesivir’s toxicity is seen.”
Schooley said he wouldn’t be surprised to learn that remdesivir manufacturer Gilead Sciences and other researchers are also studying a similar method of delivering the drug. He said he feels their process can be used with a number of drugs now limited to intravenous use.
Before the UC San Diego process is used, however, it would have to show safety and efficacy in animals, he said.
“Then we would give it to either healthy people or people who have very, very mild COVID and measure the concentrations of drugs in the bloodstream at various points in time after various doses to figure out what the best dose is,” Schooley said. “And then we would do clinical trials in people ... to see if we can help them benefit. We could be conceivably in humans over the course of the next year.”
The path forward is one already navigated by the developers of remdesivir, Schooley said, so they will be building upon that experience. In addition, he said, the course of treatment would be for five to 10 days, so researchers would be able to see fairly quickly if the oral form of the drug works.
Everyone has been focused on vaccines, Schooley said, but many researchers like them have been working on therapeutics to help people who have been infected.
“We’re excited about this step,” Schooley said, “and we are looking forward to seeing more options for people who get sick either because they haven’t been vaccinated or people who are in groups ... in which vaccines don’t work ... We just need other options.”