Prof Luke O’Neill
The breakthrough we’ve been waiting for?
SOMETHING quite remarkable happened last Wednesday evening. Tony Fauci, world-leading immunologist, key member of Donald Trump’s coronavirus task force, went on TV to announce the results of a clinical trial. A drug called Remdesivir, which is made by the company Gilead, was shown to be effective against Covid-19. I’ ll write that again. The drug Remdesivir is working in Covid-19.
On Friday it was approved for emerency use by the FDA. This is the first time a drug has been shown in a proper trial to work against Covid-19. What does this result mean and what does it hold for the future? Is this the answer we’ve all been waiting for? Or is it a little baby step in that direction? Have we reached the end of the beginning, which will mean we will bring SARS-CoV-2, the virus that causes Covid-19, to its knees and can return to the lives we once lived? I am optimistic that this is indeed the case.
THE FACTS
First, let’s look at what Tony Fauci said in that press briefing. Sitting beside him on the comfy couch was Deborah Birx, the doctor who is the coronavirus response co-ordinator for the Trump administration. She is the woman whose face fell to the floor as she heard Trump advocate the injection of disinfectant to treat Covid-19. Her face wasn’t falling last Wednesday as she listened to Fauci. It was beaming. Trump was sitting nearby with a very serious expression on his face. Maybe he’s learnt his lesson to shut up.
Fauci said: “A trial was started on February 21. It was a randomised placebo-controlled trial, comparing the Gilead drug Remdesivir to a placebo. It had about 1,090 individuals so it is the first truly high-powered trial. The primary end point was time to recovery. The study team contacted me on Monday.”
I moved to the edge of my seat. And then he said it: “The data shows that Remdesivir has a clear-cut and significant positive effect.”
These are huge words for a scientist to use: ‘clear-cut’ ‘significant’. He elaborated: “The Remdesiver-treated patients had a time to recovery of 11 days, compared to 15 days on placebo. The p-value was 0.001.” From my experience of clinical trials similar to this one (I have been involved directly in three trials for potential new medicines for inflammatory diseases), this was a remarkable result. My jaw dropped as I listened to him.
Fauci knew that other listeners may not think this a big deal, so he helped them. He said: “This is a very important proof-of-concept. A drug that can block this virus.” He also said: “The mortality rate also trended towards being better.”
The reason why all this is unprecedented is that the normal thing to do is to submit the findings to an eminent journal who has the study checked by experts (this is called peer review). Once they have vetted it, the paper is then published, and everyone can read it. And yet here was the director of America’s most important institute for infectious diseases giving us the data and his opinion of it in a press conference, with the world’s media looking on.
He explained why he was doing it. When a drug is shown to have an effect better than placebo in a serious disease, the investigators are ethically obliged to tell people who have freely volunteered to take part and who because of random selection are in the placebo group, that the drug has had an effect, to let them have access to the drug as it might save their lives. This was why he was telling us.
He went on to compare Remdesivir to another drug he had worked on, AZT. He said this was 34 years ago in a trial against HIV, the virus that causes Aids. That’s how important Fauci is. He was on the first trial for AZT. He said the results of that trial were ‘modest’ compared to the Remdesivir trial and went on to tell us that the slight effect of AZT was sufficient for it to be examined further. This led to the antiretroviral drugs that are used today to prevent people dying from Aids.
I see this as especially significant. What he was saying was Remdesivir has had such a clear-cut effect we now have a foothold against this virus. We are holding onto the cliff face for dear life. We can now start climbing up to the top, to a world where Covid-19 is a disease that is every bit as treatable as Aids.
THE FUTURE
In the next trial they will most likely try different doses or treatment regimens to optimise the effect. They will develop other drugs that look like Remdesivir that might be more potent. We are fishing in the right pond, using Remdesiver as bait. He also said that they will now embark on a trial combining Remdesivir with an anti-inflammatory drug that will protect the lungs. Just like HIV, a combination of drugs might work even better than one on its own.
He also explained that because Remdesivir blocks an enzyme in the virus that it needs to copy itself, (called RNA polymerase) other enzymes that the virus have are feasible as targets. Remdesivir was originally developed against Ebola, which has a similar RNA polymerase to
SARS-CoV-2, hence it was tried in Covid-19. He finished by saying: “Bottom line: this opens the door for treating Covid-19. It’s going to get better and better.”
Phew. I sat back. Opens the door. Better and better. Can we really dare to dream that Fauci is right?
One tiny cloud on the horizon is another trial with Remdesivir that was carried out and, as luck would have it, was also revealed last Wednesday. This almost spoiled the party. The trial showed no effect. The study has, however, been criticised for various reasons, including the fact that it mainly involved patients with severe disease. It’s well known from other anti-viral drugs that the earlier you treat the better. If you leave it too late, it’s a bit like trying to close the stable door after the horse has bolted.
This negative trial is informative, as is often the case in science. A negative teaches you something, and when we compare the two trials it may be that if you treat patients early in the disease, Remdesivir might work especially well.
Gilead, the company that makes Remdesivir, has also been accused of allowing the data to be released early to boost their share price. It is, in fact, the opposite. If Gilead had the information and didn’t release it, they might be open to accusations of insider trading.
WHAT OUTCOME?
So where does that leave us? A glimmer of hope. We’ll need to see the published data and chew over it. But I trust Tony Fauci. The man who pioneered treatments for HIV at a time when there was nothing and many lives were being lost. Does that sound familiar?
Remdesivir gives us another option should a vaccine prove difficult to develop (there is still a slim chance of that). It will buy us time in hospitals to allow doctors to learn more and come up with other ways to treat patients.
Fauci also gave us a second reason for why he was bringing us this good news. He said that he had to release the data to provide all the other trials that are running with a ‘standard of care’. This term is used all the time in medicine. It means the best possible care you can give a patient. Before this trial, there was nothing special you could give patients that would have an impact on Covid-19. Now there is. It’s called Remdesivir. It might be the very thing we’ve been looking for.
‘The mortality rate also trended towards being better’