Anti-cancer drug reduces deaths of hospitalized patients with Covid

An experimental drug initially developed to fight cancer has halved the risk of death for people hospitalized with Covid-19, a study published on Wednesday revealed.

The drug in question, sabizabulin, appears to have been more effective than others authorized for use with critically ill Covid patients. Veru, the Miami company that developed it, asked the Food and Drug Administration (FDA) for an emergency authorization to use sabizabulin. According to experts, a new weapon could be added to the modest arsenal available to hospitalized patients.

“It looks very impressive,” commented Dr. Ilan Schwartz of the University of Alberta, an infectious disease specialist who was not involved in the study. “We have a small number of possible treatments for critically ill Covid patients that reduce the risk of mortality, but one more treatment that could reduce it even further would be very welcome.”

But Schwartz cautioned that the clinical trial conducted was relatively small, with only 134 patients having received the drug. “All things considered, I find this very encouraging, but I would like to see larger, independent confirmatory studies,” he said.

Sabizabulin prevents cells from building microtubules, crucial molecular cables that send materials from one part of the cell’s interior to another.

The drug was originally developed by researchers at the University of Tennessee to fight cancer, because tumor cells depend on microtubules for their accelerated growth.

Two years ago, researchers at Veru experimented with using sabizabulin against Covid. They suspected the drug could stop the virus from replicating, which depends on the network of microtubules to assemble the pieces of new viruses.

They also theorized that the drug could help Covid patients fight potentially fatal lung inflammation. This immune reaction begins when cells recognize that they are infected and release alarm signal proteins into their surroundings. Cells need to push alarm molecules through their microtubules to get the message out.

In early 2020, researchers at the University of Tennessee Health Sciences Center found that sabizabulin suppressed 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 advanced to a final internship rehearsal.

The company sought out volunteers who were already hospitalized with Covid. To be accepted into the clinical trial, patients needed to be receiving oxygen or depending on a ventilator. They also needed to be at high risk of death from Covid, with risk factors such as hypertension, old age or obesity.

Patients were able to simultaneously receive other treatments that have already 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 most recent trial, 134 volunteers received sabizabulin and 70 received a placebo. Over 60 days, the death rate of the two groups differed markedly: 45.1% of patients in the placebo group died, compared to just 20.2% of those who received the new drug. The difference translated into a 55.2% reduction in the risk of death.

Infectologist David Boulware, from 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 justify drawing firm conclusions.

“The 45% death rate in the control group seems a little too high to me,” he commented.

Meanwhile, 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 members of the placebo group died.

Several antiviral drugs have been shown to be helpful in keeping Covid patients out of the hospital, but only if they are taken early in the illness. Paxlovid, for example, can reduce the risk of hospitalization for unvaccinated people who have risk factors for Covid by about 90%.

But these drugs don’t work well with hospitalized patients with moderate or severe Covid. That’s because they just block the viruses, rather than stopping the immune system’s runaway response.

For hospitalized patients, doctors have fewer drug options. In addition to dexamethasone and baricitinib, another anti-inflammatory drug called tocilizumab has proven to be helpful.

In April, when Veru initially announced its results, the company said it had halted the trial ahead of schedule because an independent advisory committee felt that the benefits of sabizabulin were already clear from the data and decided that it would be unethical to continue to give placebo to some patients.

Boulware acknowledged the ethical demands of the situation, but predicted that if the trial had continued longer, it is possible that sabizabulin’s benefits would have been more modest.

“Clinical trials stopped early often overestimate the effect,” he said.

He pointed out that molnupiravir, used to fight Covid, seemed to reduce Covid hospitalizations by 50%. But that number dropped to 30% in the final analysis.

Boulware predicted the same thing will happen with sabizabulin. “I doubt the effect is 55% improvement,” he said.

Translation by Clara Allain