Scientists are examining dozens of drugs as possible treatments for coronavirus. But the fortunes of one — Gilead’s remdesivir — has moved global financial markets.
As investors try to parse conflicting scientific evidence about remdesivir’s potential, here are some of the facts:
What is remdesivir?
Remdesivir is an antiviral drug that targets replication mechanisms in viruses to stop them reproducing. Gilead, a California-based biotechnology company, initially developed it to treat Ebola, another virus, but it was never approved by regulators.
Scientists began looking at using remdesivir to treat the new coronavirus because it had shown it could have an effect on other coronaviruses. They began with small studies before embarking on large, randomised clinical trials, including those run by the World Health Organization and the US National Institutes of Health.
Last month, Gilead obtained an “orphan drug” status for remdesivir from the US Food and Drug Administration. That would have extended its intellectual property protections but it is only reserved for medicines aimed at ailments affecting fewer than 200,000 people in the US. The company later backtracked, saying it had done so to speed up approval.
Why are investors excited?
Preliminary results on Wednesday from a trial by the National Institutes for Allergy and Infectious Diseases showed patients who received the drug recovered 31 per cent more quickly, in 11 days, compared with 15 for those who did not take it. The death rate was also lower, 8 per cent, compared with 11 per cent, but that was not statistically significant.
Anthony Fauci, director of the NIAID, told reporters remdesivir was not a “knockout” but that he was “very optimistic”. Establishing that a drug can target a replication mechanism inside the virus can lead to other breakthroughs, he said.
Dr Fauci compared this to his experience of the HIV epidemic, when a highly toxic drug known as AZT was first tested in the 1980s, showing only a moderate benefit. But that finding heralded breakthroughs in treatment.
Although the remdesivir data must be analysed further, Dr Fauci said it had to be announced. “Whenever you have clear-cut evidence that a drug works, you have an ethical obligation to immediately let the people know who are in the placebo group, so they could have access,” he said.
Before the NIAID trial, there were also positive signs from a New England Journal of Medicine paper based on data collected from patients taking remdesivir on a compassionate-use basis and a leak of a recording of a clinical trial investigator from the University of Chicago, saying the drug had helped most of its patients recover and be discharged.
What is the evidence it does not work?
Another trial published in the medical journal The Lancet on Wednesday, first reported by the Financial Times last week, showed disappointing results. Conducted in China, the trial showed no statistically significant benefit for those taking remdesivir: patients taking the drug recovered on average in 21 days, compared with 23 days for those on a placebo.
There may have been a slight improvement if patients took the drug early. If they took the drug in the first 10 days after they developed symptoms, they recovered in an average of 18 days. Some analysts have supported that idea — it would make sense to take an antiviral before it spread enough to wreak havoc on certain parts of the body. But the authors warned that this was still not statistically significant.
What are the problems with the trials?
Trials must enrol enough patients to be considered statistically significant. The NIAID trial enrolled more than 1,000 across the world. The Chinese study included 237 patients but it fell short of its bigger target because China contained its outbreak, so there were not enough patients to study.
They also must meet robust scientific standards to draw conclusions about what works. The Chinese trial was the first to meet these: it had a control arm in which a group of patients receive the drug and another group does not. Patients and investigators do not know who gets what, so they are called “double blind”.
Most of the studies did not have a control arm or were, like the one described in the Journal of Medicine paper, based on data that was not collected as part of a trial. Gilead published results from its own study on Wednesday, which did not have a control group, comparing people who took the drug for five days with those who took it for 10 days, making it hard to draw broader conclusions.
How does remdesivir compare with the competition?
Many other potential treatments are being investigated. They include other antivirals, such as those used against HIV, and drugs that target the body’s inflammatory reaction to the virus, such as Roche’s Actemra.
But analysts had high hopes for remdesivir based on how it has been used against Ebola and other coronaviruses. Investors also have faith that Gilead has the experience and expertise to expand manufacturing capacity and get the drug approved by regulators. Donald Trump, US president, on Wednesday said he would like the FDA to approve the drug as soon as possible. Japan signalled it would fast-track approval of remdesivir.
Some of the drugs being tested are low-priced generics — such as the antimalarial hydroxychloroquine — which do not have the intellectual property that Gilead will have to protect remdesivir as a branded drug.
Gilead has said it will not focus on profiting from remdesivir and has been providing it for free. But the company has been criticised in the past for its pricing practices, including in a dispute with the US government over one of its HIV drugs, Truvada, which is priced at more than $20,000 a year in the US. The generic version costs about $6 a month elsewhere.