The first data from the SIMPLE trial of remdesivir has been released by Gilead. Even though this is the first complete trial of the drug, it doesn't answer many questions. That's because there was no control group – something that would have been unethical for the trial participants since they had severe disease. We're just getting started.
Six weeks of endless speculation, guessing, second-guessing, ups, and downs about whether the world would have its first effective coronavirus drug has been exhausting. I see the damn molecule in my sleep.
- First, there was the speculation phase. Would Gilead's remdesivir be of any use? (Can Gilead's Remdesivir Tame The Coronavirus?) March 17
- Next, there was some encouraging news based on monkey experiments. (Will Remdesivir Work In Humans? Monkey Data Suggest Yes ) March 31
- Two weeks later - a prediction that the drug should work despite the fact that it was ineffective against Ebola, its original target. The science said yes. (Remdesivir Should Inhibit Coronavirus Despite Failing Against Ebola.) April 15
- A week later, Gilead was scaling up the synthesis of remdesivir - no easy task. A good sign? (Gilead Is Scaling Up Remdesivir. What Does This Tell Us? April 22
- The next day - an apparent failure (or is it?) is very upsetting. (What The Apparent Failure Of Remdesivir In Its 1st Controlled Trial Means, And Doesn't Mean) April 23
- If the apparent failure turns into a real failure, what does this mean for the prospects of coronavirus drug discovery? (If Remdesivir Really Fails There May Be No Treatment For Coronavirus) April 24
The first legitimate clinical data finally came out today. While the design of the trial (no control group) still leaves us with questions, according to Gilead, remdesivir has met its primary endpoint in the SIMPLE trial, which was conducted in patients with severe COVID-19 disease.
What does this mean?
It's good news, maybe very good, but in the absence of a control group (placebo), there is still no way to tell how well the drug works. Here are the highlights:
- The trials were conducted in multiple centers.
- Patients in the trials were hospitalized with severe COVID.
- The goal of the trial was to examine the optimal treatment interval.
- Some patients (200) received treatment for five days and some (197) for ten days.
- There was no significant difference between the two groups as measured by clinical improvement after 14 days. Clinical improvement was defined as an improvement of two points on a 1-7 point scale.
- Clinical recovery was defined as discharge from the hospital or no longer needing oxygen or medical care.
- A 50% clinical improvement in both groups was seen in 10-11 days.
- As to be expected with antiviral therapy, patients who got the drug earlier did better. 64% of patients who began treatment within 10 days of the start of symptoms were released from the hospital by day 14. For patients who started later, that number was 49%.
- The drug was well-tolerated
- The most common adverse events (>10%) in both groups were nausea (9-10%) and acute respiratory failure (5-day group: 6.0% vs. the 10-day group: 10.7%) (1)
- Changes in the liver enzyme ALT occurred in 7.3% of patients; 3% discontinued therapy.
This trial was not set up to gather maximum information data. It was to treat very ill patients and to examine how long to treat them. In the absence of a placebo arm, it is not possible to prove whether the drug worked at all. But, is it ethical to use a placebo in a trial of critically ill patients? I don't think so and Gilead apparently agrees. But that's coming. The SIMPLE 2 trial includes patients with moderate disease and an arm of the study consisting of standard care. Gilead is projecting that results from the first 600 patients by the end of May.
Disclaimer: My IRA contains some Gilead Stock
(1) Although acute respiratory failure is reported as an adverse event it is very likely that this arose from the disease itself, not the drug. Nonetheless, it has to be reported as an AE. This is how clinical trials work.