No need to reinvent the wheel, drug repurposing may be the fastest and cheapest way to treat people infected with the coronavirus, experts told a Tel Aviv University conference.
By Abigail Klein Leichman, ISRAEL21c
Scientists are racing to develop medications to treat people ill with Covid-19. But drug development and testing take many years and millions of dollars.
What if medications that already exist could be repurposed to tackle Covid-19?
That was the topic of a recent webinar hosted by Tel Aviv University’s Spark program, which helps move discoveries from bench to bedside, and the nonprofit MedInsight Institute, which seeks novel treatments that are safe, effective, accessible, and affordable.
Participants described the Israeli drug-repurposing scene and opportunities that could immediately benefit people infected by the SARS-CoV-2 coronavirus.
“Of the 9,000 currently approved drugs that exist globally, the potential for overcoming Covid-19 certainly exists,” said the event organizers.
“Instead of reinventing the wheel, we need to harness efforts to identify existing drugs that can treat Covid-19, select the safest ones, and validate their efficacy utilizing rapid evaluation methods tailored to times of crisis.”
Drugs with side benefits
Many older affordable generic drugs — proven safe for treating ulcers, high cholesterol, heart arrythmia, parasites, erectile dysfunction and other conditions — have multiple “side benefits” that battle effects of Covid-19, said Moshe Rogosnitzky, cofounder and executive director of the MedInsight Research Institute based in Israel and New York.
“Some of these drugs can be used alone or in combination with other drugs,” Rogosnitzky said.
The main Covid-related conditions that must be treated are respiratory failure, cardiac failure, coagulopathy (bleeding disorder), kidney failure and systemic inflammation. Each of these gets worse as the virus continues replicating.
MedInsight’s Cureiosity database collects information on off-label drug uses, diseases, symptoms and pathways.
Information mined from the database relevant for Covid conditions was published in JMIR Public Health & Surveillance.
“For example, anti-ulcer drug Famotidine, which costs about $5 per month, is cardio-protective and antiviral, and has been found recently to have anti-Covid-19 effects. It was one of the drugs used in the cocktail to treat President Trump,” Rogosnitzky said.
“Sildenafil, for pulmonary hypertension and erectile dysfunction, protects the lungs, heart and kidneys and is an anti-inflammatory,” he continued.
“Anti-cholesterol fibrates, which cost $10-$20 per month, protect the kidneys and heart, are anticoagulant, anti-inflammatory, mildly antiviral and have been found by [Hebrew University researcher] Dr. Yaakov Nahmias to have potent anti-Covid-19 effects for which clinical trials are planned,” Rogosnitzky concluded.
Nahmias, director of the university’s Grass Center for Bioengineering and its BioDesign medical innovation team, found that cholesterol-lowering drug fenofibrate (a PPAR-alpha agonist) interferes with the coronavirus’ ability to reproduce in the lungs.
He and Dr. Benjamin tenOever at New York’s Mount Sinai Medical Center reported promising results in July.
At the webinar, Nahmias said his team used retrospective clinical data to show that PPAR-alpha agonists effectively reduce risk of severe Covid-19 in people with metabolic risk factors such as obesity.
“Obesity is more of a risk factor than asthma, though this virus damages the lungs,” Nahmias said.
After studying how the virus behaves in lung cells, Nahmias’ lab used his pioneering Tissue Dynamics organ-on-a-chip technology to see the effects of the virus on metabolic processes.
“We found this SARS-CoV-2 virus causes a massive metabolic response, generating fatty acids that cause lipotoxicity in the lungs,” he said.
“We know what kinds of drugs can correct this problem, including statins and fibrates among others. Fibrates shut down the virus in five days. They can’t block the infection but can block secondary symptoms.”
His findings were validated in biopsies and data from 1,531 Covid-19 patients in Tel Aviv and Jerusalem.
“Those taking fibrates spent five fewer days in the hospital and the rate of ICU admissions dropped from about 45% to about 8%,” Nahmias reported. These patients also had reduced lung inflammation.
Three other generic cholesterol-lowering drugs — ubiquinone, ezetimibe and rosuvastatin– were found to significantly reduce risk of Covid-19 severity in a systematic analysis of electronic health records led by Dr. Ariel Israel, director of research and data at Clalit Health Services.
Mining a database of medication purchases of the HMO’s 4.5 million members, Israel’s team used statistics and probability tools to find which drugs had a coincidental protective effect on hospitalized and non-hospitalized Covid-19 patients.
“Our findings support the hypothesis that coronavirus hijacks the cholesterol synthesis pathway to boost production of cellular cholesterol it needs as an RNA virus,” Israel said.
The three generic cholesterol drugs identified “are safe and widely prescribed,” he said. Randomized controlled trials could prove their protective effects against Covid-19.
The medical records analysis also found protective effects in patients taking vitamin B12, vitamin A, zinc and magnesium.
Another presenter was Dr. Eli Schwartz, founder of Sheba Medical Center’s Center for Geographic Medicine and Tropical Diseases.
As ISRAEL21c reported in June, Schwartz launched a randomized, double-blind, placebo-controlled trial of antiparasitic drug ivermectin on 100 Israelis with mild to moderate Covid-19.
“Ivermectin is an old and very safe drug known to have antiviral properties as well. We want to see if ivermectin could prevent deterioration and virus shedding in these patients,” Schwartz said.
“Reduction of viral shedding seems to be highly important and often overlooked in mild cases.A good antiviral at the early stage of disease will stop the shedding and therefore avoid the need for isolation.”
The Israeli study is ongoing, but meanwhile an Australian study found a single ivermectin treatment caused a 5,000-fold reduction in virus after 48 hours in a cell culture. Bolivia and Peru already approved using ivermectin in Covid-19 cases.
“It’s also being used prophylactically in specific cases in Florida and in Egypt to prevent the spread of disease in families,” said Schwartz.
“Is it a magic bullet or false messiah? We don’t know yet.”
Quickly and efficiently
“Spark’s mission is to bring drugs as quickly and efficiently as possible to the clinic,” said Prof. Dan Peer, director of Spark and vice president of R&D at Tel Aviv University.
“New therapeutics and diagnostics, repurposing of existing drugs and new entities for incurable diseases can save billions of dollars and many years in development by using a pool of thousands of FDA-approved drugs.”
Peer and Rogosnitzky urge governments across the world to create task forces focused on drug repurposing.
“We should be able to solve the problem of Covid-19 by overcoming bureaucratic red tape and financial barriers to new drug development.”
You can watch the entire webinar here.