Alberta researchers are hopeful that an antiviral drug engineered to treat the deadly Ebola virus will prove a viable treatment in the ongoing fight against the coronavirus.
The drug remdesivir has already been used intravenously to treat thousands of COVID-19 patients on a compassionate basis during the escalating pandemic. Clinical trial studies began enrolling patients in early March.
Gilead Sciences — an American biotechnology company with a production facility in Edmonton — developed the drug in response to the 2014 Ebola epidemic in West Africa, where it was tested in a clinical trial.
Results showed that several other treatments were more effective against Ebola and remdesivir was discontinued as a treatment. However, testing on monkeys infected with MERS — the Middle East respiratory syndrome-related coronavirus — suggested the drug could be effective against coronaviruses.
‘A very potent compound’
The first patient diagnosed with COVID-19 in the United States received remdesivir for compassionate use, which allows the use of an unapproved drug to treat a seriously-ill patient when no other treatments are available.
The patient had been admitted to the intensive care unit and received the drug on the seventh day of illness. The next day the patient showed a marked improvement and his symptoms eventually disappeared altogether.
If proven effective, remdesivir would be one of the few available remedies for a respiratory illness which has killed thousands of people around the world.
Anecdotal evidence and promising results in animals trials make the drug a strong candidate for clinical trials, said Matthias Götte, chair of the medical microbiology and immunology department at the University of Alberta.
Götte has been working with his team to find out how the drug may be used to treat coronaviruses.
An attack from the inside
His study, published in the Journal of Biological Chemistry in late February, was among the first in Canada to examine the COVID-19 strain, and explore why remdesivir might be an effective treatment.
“We know the drug works against different coronaviruses, like MERS and SARS, and we know the novel coronavirus is very similar to SARS,” Götte said.
“The pre-clinical data looked very good. It was a very potent compound so we were interested in the actual mechanism, how that drug actually works against Ebola.
“We created a synthetic version of this enzyme and, in a test tube, we were able to study the mechanism of remdesivir against this Ebola target.”
Götte’s research shows that the drug stops the virus from replicating. It disrupts the viruses biochemistry by masquerading as a part of the virus itself.
“Remdesivir essentially mimics one of the natural building blocks for RNA synthesis necessary for genome replication of the virus,” Götte said.
“Enzymes within the virus are synthesizing the viral RNA genome with these building blocks, but they mix up the bits they need with the drug. Once the drug is incorporated into the growing RNA chain, the virus can no longer replicate.”
Last week, Gilead Sciences announced two clinical studies to evaluate the safety and efficacy of remdesivir in about 1,000 adults diagnosed with COVID-19. The company said the randomized studies will begin this month in countries across Asia and in other countries where COVID-19 has been diagnosed in higher numbers.
This drug is quite potent against it’s target but that does not necessarily translate into success in clinical trials.– Matthias Gotte.
Götte said no matter the results of the studies, his team will continue to examine how the drug interacts with the new virus. The results of the clinical trial will be only the first step in finding an effective treatment, and one drug will likely not be enough.
“Ideally, we will have a couple of drugs because certain strains could be resistant to certain treatments,” Götte said.
He will be anxiously awaiting the results of the ongoing clinical trials which could be available as early as May.
“One thing is clear. This is not a cure,” Götte said. “We have to wait for the clinical trial results. That’s the gold standard and we have to be patient.”
“This drug is quite potent against it’s target but that does not necessarily translate into success in clinical trials.”
Meanwhile, Gilead, overwhelmed by demand for the experimental treatment, abruptly shut down its emergency access program this week.
The company said it was setting up a broader access program that could try to help more sick people but its current program is unprepared to handle the current health crisis.
“We recognize that there are severely ill patients who are unable to enrol in clinical trials and for whom no approved treatment options are effective,” reads a statement from the company.
“Gilead has been working with regulatory agencies to provide remdesivir to these patients where feasible.”
To date, the company said it has provided emergency access to remdesivir for several hundred patients in the United States, Europe and Japan.
Health Canada had also been considering special access requests for the drug on a patient-by-patient basis.
“In recent weeks, there has been an exponential increase in compassionate-use requests for emergency access to remdesivir, related to the spread of the coronavirus in Europe and the United States,” reads the statement from Gilead.
“This has flooded an emergency-treatment-access system that was set up for very limited access to investigational medicines and never intended for use in response to a pandemic.”