After 18 months of dedicated work by scientists and doctors from around the world, promising results of new drugs to treat COVID-19 are starting to be released.
Israel has played – and continues to play – a significant role in the fight for a cure for corona.
Earlier this month, the American companies Merck and Ridgeback Biotherapeutics announced that they had applied for emergency use authorization from the United States Food and Drug Administration for their oral antiviral medicine Molnupiravir.
The drug, when given within the first five days of the onset of the virus, was found effective for the treatment of mild-to-moderate COVID-19 in adults who are at risk of progressing to severe illness and possible hospitalization.
Merck submitted Phase III trial data that was conducted at dozens of clinics around the world. It showed that Molnupiravir reduced the risk of hospitalization or death by approximately 50%.
The first patient to be given Molnupiravir during its Phase II trial was in Israel at Hadassah University Medical Center, under the oversight of Prof. Yossi Caraco.
“In the beginning, everyone was focused on the really sick patients,” Caraco recalled. “I thought the approach of [targeting] moderate patients would be beneficial and was really eager to take part in this study. We were chosen.”
Caraco led the Phase II study for Merck (legally known as MSD in Israel), which ran from late fall of 2020 through April 2021. Caraco presented the data from this trial at the European Congress of Clinical Microbiology & Infectious Diseases in July, shortly after the Phase III trial was launched.
The last phase did not include Israel, Caraco said, mainly because the country had few eligible participants, since the majority of Israeli adults are vaccinated.
Only a few days after Merck made its announcement, an American-Israeli company also shared analysis of its Phase II/III trial of a drug targeting moderately severe patients – people who were receiving oxygen support and had pneumonia.
RedHill Biopharma, the developer of Opaganib, showed that its drug resulted in a statistically significant 62% reduction in mortality of COVID-19 patients versus treatment with a placebo.
Opaganib is an oral antiviral and anti-inflammatory pill.
Patients left the hospital a median of four days earlier when they took Opaganib – a cumulative saving of 524 days of hospitalization across the group of 251 study participants who received the treatment by day 42.
Specifically, patients treated with Opaganib showed a median time of 10 days to discharge versus 14 days for the placebo group.
Finally, it also showed statistically significant improved outcomes in time to room air: Some 77% of Opaganib-treated patients reached room air by day 14 versus 63.5% for placebo.
In total, 475 people were enrolled in the study. Participants were randomized at a 1:1 ratio to receive either the drug or a placebo on top of standard-of-care therapy.
The company’s Chief Operating Officer, Gilead Raday, said that RedHill is already in discussion with the FDA to determine the next steps, as it continues to analyze the results of the Phase II/III trial. He said the company will discuss the date with European Medicines Agency and to the regulatory bodies of some of the other countries that were included in the study, including Israel, for emergency approval.
“We are really proud to have completed this study,” Raday said.
Two other relevant announcements were also made in the last month or so, the first by Todos Medical, a medical diagnostics company located in Rehovot and New York.
The company announced in mid-September that it had received a notice of allowance from the US Patent and Trademark Office for a trademark covering its oral antiviral drug known as Tollovir.
The company completed a successful Phase I trial in 2020 evaluating the safety and efficacy of Tollovir in collaboration with NLC Pharma Israel. Todos and NLC are now enrolling patients in a Phase II clinical study in Israel of hospitalized patients and finalizing the details of a Phase II/III study of both hospitalized and non-hospitalized patients that should be ready soon.
Tollovir aims to inhibit the 3CL protease, the main protease found in coronaviruses and their fundamental reproductive mechanism.
“While we are pushing forward with our efforts to complete ongoing clinical studies in Israel and initiate pivotal studies in India, we are also very focused on engaging the US FDA to evaluate Tollovir potentially as part of the emergency use authorization pathway,” Todos Medical President and CEO Gerald Commissiong said.
He added that the results from the first clinical trial are being readied for release.
Finally, the Israeli Patent Office issued a new patent earlier this month covering the immunotherapy drug Allocetra, the brainchild of Hadassah’s Dr. Dror Mevorach, which is being developed by the clinical-stage company Enlivex Therapeutics.
Allocetra is meant to treat a wide range of cases in which there is an overreaction of the immune system, which leads to an increase in the secretion of proteins by cells of the immune system called cytokines and causes a cytokine storm. As such, in addition to use against COVID-19, it has been successfully tested on sepsis and bone marrow transplant patients.
A cytokine storm is when the immune system essentially goes into overdrive and begins attacking healthy cells.
Enlivex is currently conducting two parallel controlled studies of Allocetra in treating COVID-19 and septic patients.
“One of the best things that we see is that we were able to significantly shorten the time at the hospital for these patients,” Mevorach told the Post earlier this year, shortly after a handful of COVID-19 patients received the experimental treatment in a first trial. “We could significantly reduce the burden on Israelis hospitals and those in other countries.”