Cancer drug drastically cuts death toll in hospitalized Covid patients
An experimental drug originally developed to fight cancer has halved the risk of death for people hospitalized with Covid, according to a study published on Wednesday.
The drug, sabizabulin, appeared to be more effective than others that have been licensed for critically ill Covid patients. Veru, the Miami company that developed the drug, has applied to the Food and Drug Administration for emergency clearance for its use. It would potentially add a new weapon to the modest arsenal available to hospital patients, experts said.
“It 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 welcome.”
Dr Schwartz cautioned, however, that the trial was relatively small, with just 134 patients receiving the drug. “Overall, I think it’s very exciting, although I would welcome larger, independent, confirmatory studies,” he said.
Sabizabulin prevents cells from building microtubules, critical molecular cables that carry 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, as fast-growing tumor cells depend on microtubules for their rapid growth.
Two years ago, researchers at Veru tried sabizabulin on Covid. They suspected the drug might prevent viral replication, which depends on the microtubule network to pull together the pieces of new viruses.
They also speculated 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 must push alarm molecules along their microtubules to get the message across.
In early 2020, researchers at the University of Tennessee Health Sciences Center found that sabizabulin dampened these warning signals in mouse cells. A few months later, Veru began testing the drug, which comes in pill form, in humans. In May 2021, he moved to an advanced stage trial.
The company sought out volunteers who were already in hospital for Covid. To be eligible for the trial, patients had to be receiving oxygen or relying on a ventilator. They also had to be at high risk of dying from Covid, with risk factors like hypertension, advanced age or obesity.
Patients were allowed to concurrently receive other treatments that have been shown to be effective in saving the 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% of the placebo group died, compared to only 20.2% of those who received the new drug. This difference translated into a 55.2% reduction in the risk of death.
Dr David Boulware, an infectious disease expert at the University of Minnesota, warned that the large number of deaths in the placebo group could be a sign that the study was too small to draw definitive conclusions.
“The 45% mortality rate in the control group strikes me as being rather high,” 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% of the placebo group died.
A number of antiviral drugs have proven effective in keeping Covid patients out of hospital, but only if given early in their illness. Paxlovid, for example, can reduce the risk of hospitalization for unvaccinated people with Covid risk factors by around 90%.
These drugs do not work well on hospitalized patients with moderate to severe Covid, however. This is because they only block viruses, rather than dampen the immune system’s response out of control.
For hospitalized patients, doctors have fewer drugs to choose from. In addition to dexamethasone and baricitinib, another anti-inflammatory drug called tocilizumab has been shown to be effective.
When Veru initially announced its results in April, the company said it had terminated the trial prematurely because an independent advisory board had found that the benefits of sabizabulin were already clear from the data; it would be unethical, they decided, to continue giving some patients a placebo.
Although Dr. Boulware acknowledged the ethical demands of the situation, he also predicted that had the trial lasted longer, the drug’s benefits might have appeared more modest.
“Trials that are stopped early consistently overestimate the effect,” he said.
Dr Boulware noted that the Covid drug molnupiravir initially appeared to reduce the risk of hospitalization from Covid by 50%. But this figure fell to 30% in the final analysis.
He predicted a similar fate for sabizabulin. “I would be skeptical if the effect was 55%,” Dr. Boulware said.