Fierce Biotech: Remdesivir “flops” in first placebo-controlled trial, but study terminated due to low enrollment; patients treated too late

flip flop sandals by Peggy Choucair courtesy of pixabay.com

First reports by the Financial Times today (April 23) of a remdesivir placebo-controlled trial in China say it was a “flop”.  Virtually the same percentage of mortality was found– 13% vs. 14%– with 158 on remdesivir and 79 on a placebo; 18 were withdrawn due to side effects in the active group and an unspecified number (in the FT story) withdrawn from the placebo arm for side effects (this sounds absurd, but is expected in such a trial, in which even the doctors giving the pill don’t know whether it’s a placebo or the real thing).

Fierce Biotech ran a story on the same study and reached somewhat different conclusions.  First, “Patients in both study arms experienced side effects at roughly the same rate (about 65%), but more patients on remdesivir stopped treatment early because of side effects compared with placebo (12% versus 5.1%).”  Make of that what you will.  Second, Gilead’s chief medical officer said,  “The study was terminated early due to low enrollment, and, as a result, it was underpowered to enable statistically meaningful conclusions.”

Third, patients were treated as late as twelve days after onset of symptoms.  This is too long; most infection treatments don’t help unless they are started early.  For example, Tamiflu, which is available by prescription for influenza, says in its prescribing information (wording required by the FDA) that the drug must be started within 48 hours to have a significant beneficial effect in shortening the illness.  This restriction makes sense, because the influenza virus (like most viruses) replicates rapidly in the early phases of disease; by the time symptoms are evident, the body has already started to react to the infection and replication rates are already dropping.  To have any effect, the drug must interfere in the rapid replication phase and be started as soon as symptoms begin.

All of this does not say that remdesivir will work, even if it is started early.  But this warning suggests that we should  beware of studies that are done of people who don’t start taking the medicine until they are already in the recovery (and body reaction) phase of the disease.

Currently, the National Institute for Allergy and Infectious Diseases is conducting a study of remdesivir in COVID-19, and Gilead is conducting additional placebo-controlled (phase III) studies as well.  Only time will tell whether remdesivir is beneficial.  In the meantime, the stock-buying public is getting a crash course in medicine.