An international trial has found an amazing reduction in mortality in seriously ill, old, fat people (the most vulnerable to Covid death).
The new drug has a fascinating mechanism.
https://www.medpagetoday.com/infectiousdisease/covid19/99610…
Whopping Mortality Benefit in Severe COVID Trial
— Oral sabizabulin showed 55% reduction in risk for death in hospitalized patients
by Ian Ingram, Managing Editor, MedPage Today, July 7, 2022
…
Mortality at 60 days, the international trial’s primary endpoint, was more than halved in the group assigned to investigational sabizabulin versus those randomized to placebo (20.2% vs 45.1%, P=0.0042)…Outcomes in key secondary endpoints landed in sabizabulin’s favor as well, with significantly fewer average days spent in the intensive care unit (ICU; 17 vs 31 in the placebo group), on mechanical ventilation (14 vs 29), and in the hospital (26 vs 35)…
“Sabizabulin is an orally available, novel microtubule disruptor that targets, binds, and crosslinks both the a- and ß-tubulin subunits to inhibit polymerization and to induce depolymerization of microtubules in cells,” noted Barnette and colleagues.
“Microtubules are intracellular transport structures critical for coronavirus cellular entry, trafficking, replication, and egress as well as for triggering the innate inflammatory response and cytokine storm responsible for ARDS, septic shock, and frequently death,” the group added… [end quote]
Neat, huh?
First, notice the extremely high mortality rate of 45% in the control group of this trial. The patients were selected to be very sick to start with. Almost all were already on oxygen. Most had serious co-morbidities and were at high risk for acute respiratory distress syndrome (ARDS) or death. By comparison, mortality rates at similar time points among the control arms of trials involving hospitalized COVID-19 patients have ranged from 7.8% in ACTT-2, 15.2% in ACTT-1, to 25.7% in the control group of the segment of the RECOVERY trial that led to dexamethasone being established as a standard treatment in this setting. The high mortality rate of the control group in this new trial shows how much sicker they were on average.
Sabizabulin appears to be snatching patients out of the jaws of death itself.
How does it work?
Cells contain many tiny organelles which are dedicated little factories for various cell processes (e.g. mitochondria, ribosomes, etc.) which need to move molecules from one place to another. The cytosol (the gel that fills the cell) is rather hard to move through. The cell contains a network of microtubules that act like roads to help transport molecules and other items around the cell.
https://www.nature.com/scitable/content/microtubules-the-bas…
https://en.wikipedia.org/wiki/Microtubule
Microtubules are important in bringing the coronavirus into the cell, assembling new copies of virus, and bringing the new viruses to the outside of the cell.
The new drug disrupts the assembly of new microtubules that the virus needs to enter and assemble new viruses. It can also disrupt existing microtubules. Not surprisingly, there were many adverse events.
The mortality advantage in the U.S. branch of the trial was 55% but unfortunately they didn’t report vaccination status.
Hard to say how long it will take to get approval, rev up manufacturing and bring this new drug into widespread clinical use.
Wendy