An experimental drug initially developed to fight cancer has halved the risk of death for people hospitalized with covid, according to a study published Wednesday.
The drug, sabizabulin, appeared to be more effective than others that have been licensed for severe covid patients. Veru, the Miami company that developed the drug, has applied to the Food and Drug Administration (FDA) for an emergency authorization for its use. That would potentially add a new weapon to the modest arsenal available to hospitalized patients, experts said.
“This looks super impressive,” said Dr. Ilan Schwartz, an infectious disease expert at the University of Alberta who was not involved in the study. “We have a small number of treatments for patients with severe disease that improve mortality, but another treatment that can further reduce deaths would be very welcome.”
However, Dr. Schwartz cautioned that the trial was relatively small, with only 134 patients receiving the drug. “Overall, I think this is very exciting, although I would welcome larger, independent confirmatory studies,” he said.
Sabizabulin prevents cells from building microtubules, critical molecular cables that transport material from one part of the cell interior to another.
The drug was originally developed by researchers at the University of Tennessee to fight cancer because fast-growing tumor cells depend on microtubules for rapid growth.
Two years ago, Veru researchers tested sabizabulin on Covid. They suspected that the drug might prevent viral replication, which relies on the network of microtubules to join the pieces of new viruses.
They also hypothesized that the drug would help Covid patients fight life-threatening lung inflammation. This immune response begins when cells recognize that they are infected and release alarm signal proteins into their environment. Cells have to push alarm molecules along their microtubules to get the word out.
In early 2020, researchers at the University of Tennessee Health Science Center found that sabizabulin attenuated these alarm signals in mouse cells. A few months later, Veru began testing the drug, which is taken in pill form, on people. In May 2021, she progressed to a late stage test.
The company looked for volunteers who were already in the hospital for Covid. To be eligible for the trial, patients had to be on oxygen or ventilator dependent. They also had to be at high risk of dying from Covid, with risk factors such as high blood pressure, advanced age or obesity.
Patients were allowed to simultaneously receive other treatments that have been shown to be effective in saving lives of hospitalized Covid patients. A steroid called dexamethasone, for example, reduces the risk of death by a third.
In the latest trial, 134 volunteers received sabizabulin and 70 a placebo. Over the course of 60 days, the death rates of the two groups were significantly different: 45.1 percent of the placebo group died compared to just 20.2 percent of those given the new drug. That difference translated into a 55.2 percent reduction in the risk of death.
Dr. David Boulware, an infectious disease expert at the University of Minnesota, cautioned that the large number of deaths in the placebo group could be a sign that the study was too small to draw firm conclusions.
“The 45 percent mortality rate in the control group seems pretty high to me,” he said.
By contrast, in a trial of an arthritis drug called baricitinib, researchers gave the drug to 515 Covid patients, while 518 received a placebo. Only 7.8 percent of the placebo group died.
Several antiviral drugs have been shown to be effective in keeping covid patients out of the hospital, but only if they are given early in the course of their illness. Paxlovid, for example, can reduce the risk of hospitalization for unvaccinated people with risk factors for covid by about 90 percent.
However, these drugs do not work well in hospitalized patients with moderate to severe covid. This is because they only block viruses, rather than slowing down a runaway immune system response.
For hospitalized patients, doctors have fewer medications to choose from. In addition to dexamethasone and baricitinib, another anti-inflammatory drug called tocilizumab has been shown to help.
When Veru initially announced its results in April, the company said it stopped the trial early because an independent advisory committee found that sabizabulin’s benefits were already clear from the data; They decided that it would be unethical to continue to give some patients a placebo.
While Dr. Boulware acknowledged the ethical demands of the situation, he also predicted that if the trial had lasted longer, the drug’s benefits might have been more modest.
“Trials that are stopped early routinely overestimate the effect,” he said.
Dr. Boulware noted that the anti-Covid drug molnupiravir initially appeared to reduce the risk of hospitalization for Covid by 50 percent. But that number dropped to 30 percent in the final analysis.
He predicted a similar fate for sabizabulin. “I would be skeptical that the effect is 55 percent,” Dr. Boulware said.