Molnupiravir is being hailed as a potential breakthrough in the global fight against COVID-19. The new antiviral pill, developed by pharmaceutical giant Merck & Co., has been found to effectively treat mild and moderate cases, cutting the risk of hospitalization and death by half.
On the heels of results from its Phase III trial, Merck said it would seek U.S. emergency use authorization. If approved, molnupiravir would become the first oral antiviral medication for COVID-19 and could mark a turning point nearly two years into a pandemic that has cost millions of lives.
So why has it taken so long to develop an effective and simple treatment? According to Shy Arkin, a professor of structural biochemistry at the Hebrew University of Jerusalem, it’s complicated.
“Viruses are quite tricky,” Arkin said. “There are many viruses that still don’t have vaccines despite our very best efforts; HIV is one good example and Hepatitis C is another. But for both of those, we have drugs. Then there are other viruses where we have vaccines and we don’t have drugs.”
Arkin and a team of researchers are presently working on repurposing existing approved drugs to treat COVID-19. They have already screened roughly 3,000 different drugs in a lab and identified three “very good candidates.”
The first – darapladib – was originally developed by GlaxoSmithKline to treat atherosclerosis, but failed in Phase III trials after it was found not to be efficacious against that disease.
Arkin recently discovered that it inhibits viral activity in COVID-infected tissue cells. “It’s safe to use but was not efficacious against atherosclerosis,” said Arkin.
The second drug that was found to be effective is called flumatinib, an anti-cancer drug that is only approved in China.
So far, Arkin said, both darapladib and flumatinib appear to be “equally as effective” as molnupiravir in treating COVID-19, however further research remains to be done. Specifically, the Hebrew University team will be starting animal model trials in the coming days to confirm their initial results.
“The two drugs that we have identified were known to us and our screening was basically finished about a year ago,” Arkin said. “But there’s only one site in Israel that can conduct these experiments so we needed to go overseas and the number of contract research organizations that actually can conduct these is literally a handful. … Merck with its endless resources can obviously move far, far faster than we can.”
“The U.S. government poured huge amounts of resources on vaccine development and meager, if any, resources on drug development,” Arkin said.
Like Arkin, other Israeli researchers working on developing COVID treatments also cited difficulty in pinning the virus down. “When you’re trying to study COVID-19 and trying to ask whether your drug has an effect, all of the studies that are carried out on mild or medium patients, they won’t be able to show significance,” Prof. Yaakov Nahmias, director of the Grass Center for Bioengineering at the Hebrew University of Jerusalem, said.
“Most of these patients are going to recover anyway,” Nahmias said. “These [patients] actually don’t really need to be hospitalized and can receive antibiotics treatment and be released home. The only patients that really need to be hospitalized are those that require respiratory support, where their oxygen (levels) in their blood drops below something like 93%.”
While the vast majority of those who contract COVID end up with only mild or moderate disease, Nahmias and his team have decided to focus their efforts entirely on severe cases.
In an investigator-initiated interventional open-label clinical study whose findings were released in late August, Nahmias and his research team administered 145 mg/day of Tricor (fenofibrate) to 15 patients hospitalized with severe COVID-19 over a period of 10 days and repeatedly monitored their disease progression.
The clinical outcomes of the study were dramatic: 14 out of 15 patients, or 93.3%, no longer required respiratory support after five to seven days of treatment, compared to 28.5% of patients in a historical control group. The final patient also eventually recovered and ended up being released sometime later.
“What we saw is that their inflammatory markers dropped very, very fast,” Nahmias said. “Within 48 hours of receiving the drug, they simply didn’t have inflammation at all.
While the early results for Tricor are very promising, further study must be completed before the drug becomes more widely available as a COVID treatment. In fact, Phase III clinical trials are slated to be completed within several months.
The article was written by Maya Margit and reprinted with permission from TheMediaLine