Almost 10 different vaccines to prevent infection with COVID-19 are being given or are in clinical trials, but so far there has been no medication proven to effectively treat patients with the advanced disease. But now, a newly developed drug developed in Israel – although in the early stages of experimentation – offers some hope. 

The drug developed at Tel Aviv Sourasky Medical Center by Prof. Nadir Arber of Tel Aviv University’s Cancer Biology Research Center has been tested in small, multi-center clinical trials on a total of 30 patients in moderate-to-critical condition in Coronavirus intensive care units. The condition of 29 was good enough for them to be discharged from hospital in just three to five days.  The 30th patient also recovered but it took a longer time. The potential treatment was given as part of 28-day Phase I clinical trials. 

The drug, named EXO-CD24 or Allocetra therapy, was developed by the Enlivex Therapeutics immunotherapy company in the Israeli city of Nes Ziona (the same city in which Israel’s COVId-18 experimental vaccine is being developed). Most of the patients in the trials had preexisting risk factors including obesity and hypertension, the company said. Allocetra is designed to treat the severe condition in which the immune system itself attacks the body. At this stage, the virus that caused the disease may no longer be active or even present in the body, but the immune reaction cannot be stopped. Enlivex’s product was developed to control the immune system and prevent it from running wild. It was originally developed to deal with sepsis following other infections before the coronavirus pandemic hit, but the immune system works in a similar way irrespective of the source of infection.

COVID-19 has two main stages: The first is similar to influenza and does not require specific treatment but only supportive care. The second occurs in 5% to 7% of patients and is characterized by overactivity of the immune system – a “cytokine storm.” 

“Even if the vaccines perform their function and even if no new mutations are produced, the disease will remain with us,” said Arber. “To this end, we have developed a unique drug. EXO-CD24. About six months passed from the moment the idea was conceived and the technology was invented until it was first tested in humans, in the first clinical phase,” noted Arber, one of the hospital’s prominent doctors and researchers who led in the development of the drug over a period of many years.

“The drug is based on exosomes released from the cell membrane and used for intercellular communication. We enrich the exosomes with 24CD protein. This protein is expressed on the surface of the cell and has a known and important role in regulating the immune system,” explained Dr. Shiran Shapira, head of Arber’s molecular genetics lab who has been involved in research on CD24 protein for over two decades.

The preparation is given by inhalation, once a day, for only a few minutes, over a period of five days. “The uniqueness of the preparation lies in a double mechanism that acts to inhibit the action of the pathway leading to the immune storm and the multiple secretions of cytokines. The preparation is directed directly to the center of the cytokine storm in the lungs, so that unlike many other preparations in the world that are given systematically and selectively inhibit a particular cytokine but cause severe and multiple side effects, EXO-CD24 is given topically, works extensively and has no side effects. This is an advanced preparation that can be produced quickly and efficiently and at a very low cost, which could be produced in every pharmaceutical facility in the country. It could be made available around the world after it is approved by the drug regulation authorities,” said Arber.

Sourasky director-general Prof. Ronni added that “Prof. Nadir Arber is a talented researcher and physician. The research carried out in his laboratory is innovative and sophisticated and could save Corona patients. His results for Phase I research were excellent and gave us confidence in the method he has been researching in his lab for many years.” 

Following the successful Phase I trial, the company expects to submit a summary of the data to regulatory bodies later this month to serve as the basis for a discussion on the next steps in Allocetra’s regulatory pathway in COVID-19 patients with severe or critical COVID-19.

Prof. Vernon van Heerden, head of the general intensive care unit at Hadassah University Medical Center in Jerusalem and the lead investigator of both the prior-Phase Ib and the now-completed Phase II clinical trials of Allocetra in severe and critical COVID-19 patients told the business daily Globes: “The results we have seen from COVID-19 patients treated to date with Allocetra are exciting. The Phase I patients who have been discharged from the hospital are currently healthy. We believe that these compelling results have demonstrated the safety and efficacy of Allocetra in these complicated patients, highlighting the potential of Enlivex’s product candidate to benefit severe and critical COVID-19 patients as well as others suffering from cytokine storms and organ dysfunctions across various clinical indications.”

Prof. Dror Mevorach, the chief scientific and medical officer of Enlivex, added: “We believe the results from the COVID-19 clinical trials of Allocetra represent a unique opportunity for severe and critical COVID-19 patients on top of standard of care. The data suggest that Allocetra may have utility as a safe and efficacious treatment for reprogramming macrophages and resolving states of organ failures both in this COVID-19 patient population, regardless of the specific coronavirus mutation that inflicted the patients, and across different life-threatening, high mortality clinical indications with high unmet medical needs.”

Dr. Oren Hershkovitz, chief executive officer of the company, concluded: “We are pleased with the top-line results of the clinical trial. We believe that Allocetra, if approved, could potentially cover the void that currently exists for the treatment of severe and critical COVID-19 patients. COVID-19 vaccines are game-changers in the fight against the pandemic, yet with various surveys demonstrating 25-32% of the population in the US and major European countries unwilling to get vaccinated, and concerns surrounding various mutant strains of the SARS-CoV-2 virus, our commercial model estimates continued demand for the treatment of severe and critical COVID-19 patients for years to come.”