Merck’s new antiviral pill, Molnupiravir, cuts the risk of hospitalization and death due to COVID-19 by half.
At least, that’s what a randomized clinical trial of 775 patients shows. No deaths were identified in those receiving Molnupiravir, compared with eight deaths among those receiving a placebo. Treatment was started early after initial symptom onset with an easy five-day course of twice-daily pills.
If approved by the Food and Drug Administration, COVID-19 patients will be sent home armed with a defense means. Because Molnupiravir prevents viral replication by introducing errors into the virus’s genetic code (rather than just target the mutating spike protein), Molnupiravir will likely remain effective against current variants such as Delta and future variants.
Sounds like a very promising breakthrough. One that should prompt all of us to ask: What took so long? Was there a faster route to finding successful oral treatments that we didn’t take? Are we still making the same mistakes that block future breakthroughs?
Work on Molnupiravir started in 2003 at Emory and matured over the next decade into an effective orally available pill that could be self-administered, making it useful for viral diseases that are widespread and have an acute onset. The drug is rapidly distributed to the lungs to treat viral infections and crosses the blood-brain barrier to manage central nervous system viruses. The quick onset of activity works within the narrow window of opportunity for treatment offered early during infections.
Fast forward to 2019.
Researchers were excited enough to prepare an FDA investigational new drug application to combat influenza, another RNA virus like SARS-CoV2. When COVID-19 hit, investigators seamlessly pivoted to a Phase I safety trial to demonstrate tolerability in humans. Within nine weeks, results from the Phase I study showed the drug had “good oral bioavailability, was well tolerated, and had a good safety profile,” according to investigator George Painter, Ph.D.
After this promising start, Pharma giant Merck joined the effort to accelerate research on a potentially lifesaving pill for those infected with COVID-19.
But this is where the timeline bogs down.
Over the next year, only 175 participants with confirmed COVID-19 diagnoses were recruited. When the data were presented at a national meeting in April, no infectious virus could be grown from nose swabs taken from participants who received Molnupiravir at a five-day follow-up. In comparison, 24% of participants who received a placebo still had an infectious virus on nose swabs at day five, a statistical difference.
The drug affected early-stage disease and likely transmission. While private-sector researchers labored to recruit patients at a rate of under two per day, the U.S. government fast-tracked mRNA vaccines that recruited 75,000 over a few months at a rate close to 1,000 per day. The glacial recruitment pace for the pill option continued until the Phase 3 trial’s spectacular benefits were so clear that the trial was halted early, as continuation was deemed unethical.
How did the search for a pill solution fall so far behind? Some argue we took our eyes off the prize in our single-minded pursuit of effective vaccines. An “Operation Warp Speed” equivalent focused on oral therapies for early treatment would have turbo-charged this effort. Merck worked outside of U.S. government trials to accelerate recruitment and still toiled for 20 months until this week’s news.
At the same time, political infighting clouded our vision as some treatments were seen as belonging to the other team. We should have been rooting for all the treatments and using trials to differentiate between winners and losers rigorously. But the biggest obstacle is the general reluctance of people to participate in clinical trials. Both of us have participated in large national trials. We have seen firsthand that volunteer enrollment rates are painfully slow.
Add the confusion and noise around COVID-19 treatments into the mix, and patient participation slows to a crawl. Assessing the many remaining oral pill options in well-funded clinical trials, including repurposed FDA-approved medications, should be a major focus of our public health leaders.
So, let’s start today. If you are diagnosed with COVID-19, go to ACTIV 6 or COVID-OUT and see if you can help yourself and your fellow citizens by participating in high-caliber trials. Our learnings will help tame the pandemic and prepare for future ones on the horizon.
