Keeping track of all the research going into Covid-19 treatments is a challenge. The studies that grab the headlines are not always the best, and hundreds of others languish in obscurity. To address this, a team at the University of Pennsylvania have created a database of all trials using medications previously approved for other conditions. They've also published the first paper analyzing this data in Infectious Diseases and Therapy.
Getting a new drug through safety trials is a slow process, so the focus of Covid-19 trials has been on those already licensed for use. Even if they come with serious side-effects, these are known and have been judged acceptable in the right circumstances.
Re-purposing drugs is familiar territory for lead author Dr David Fajgenbaum. Eight years ago, Fajgenbaum was a young medical researcher who found himself stricken with idiopathic multicentric Castleman disease, a rare and often fatal inflammatory disorder. After multiple brushes with death, Fajgenbaum set about identifying cellular malfunctions that could be causing his condition and used this to identify an existing drug that might help him. The drug, Sirolimus, saved his life and is now helping others with Castleman disease.
“We can’t win this fight if we don’t take stock of the tools that are already being used and search for new ones that could be effective,” Fajgenbaum said in a statement. “With the world facing its greatest public health crisis in a century, we decided to take action, using the same approach that helped me and applying it to potentially help find promising leads in the treatment of Covid-19.”
A constantly updated database, currently with 44,000 patients, is available at the Covid Registry of Off-label & New Agents (CORONA). The initial paper combined the 146 suitable studies conducted before March 27. These included more than 9,000 patients, most of them in China since the virus was just starting to take hold elsewhere at that point.
Unsurprisingly, known antivirals were the most common category, including 72 percent of patients in the studies, although many also had treatments from other drug classes. This original tranche included 2,000 patients who received Lopinavir/ritonavir, which has failed to match hopes, while just 114 had been given Hydroxychloroquine or chloroquine, soon becoming easily the highest-profile treatment.
Among the most common treatments the paper reports were those given Interferon for an average of 10 days before their symptoms resolved, while those given Oseltamivir took almost twice as long, with other drugs in-between. However, the studies in the paper were observational, rather than controlled trials. Consequently, those given certain drugs may have started off sicker than those in other trials, making comparisons far more complex than these figures might suggest. Rather than revealing one drug's success, the study's main role is to provide a pointer as to which medicines deserve deeper investigation.
“The major changes that have occurred since I submitted are that some of these drugs have actually been evaluated in formal clinical trials," Fajgenbaum told IFLScience. "It is much more difficult to understand how well a drug is working when there is no comparison group. This is particularly important for a disease like Covid-19 …[where] many patients will recover without treatment.”
Of the more than 160 drugs that have been tried so far, Fajgenbaum considers several promising: “Tocilizumab and siltuximab are two drugs I am really optimistic about based on early studies and their mechanisms of action.”
However, none are close to being definite winners yet. Faigenbaum calls himself “living proof” of re-purposed drugs' potential, using his recent book to spread the word on this sort of research.