COVID-19 Drug Nears Pivotal Late-Stage Trial

Targeting Fatal Cytokine Storms

Five doses of a drug given to patients with moderate to severe COVID-19 before they require ventilation may drastically improve their chances of recovering from COVID-19, according to results in May from a set of Phase 1 trials in Israel, reported Sharon Wrobel of Algemeiner.

EXO-CD24, developed by Tel Aviv’s Ichilov Medical Center is an experimental treatment given once daily by inhalation for only a few minutes, over the course of five days. It has successfully prevented clinical deterioration of 30 moderate to severe COVID-19 patients in the clinical trial. The inhaler drug is being tested in a second round of clinical tests in Greece, where as many as 90 COVID-19 patients are expected to enroll, according to Professor Nadir Arber, who leads the drug’s development at Ichilov. He expects to file applications for emergency use authorization of EXO-CD24 with the US Food and Drug Administration (FDA) and other regulatory bodies by the end of 2021 or the beginning of 2022.

According to Arber, “We can definitely declare that the drug is safe and has no side effects. We are very optimistic about the recovery of the patients in Greece where we are testing different doses of the drug. We expect the trial to be completed by the end of July.”

EXO-CD24 is a targeted experimental drug that was developed to fight the second phase of COVID-19. It was predicated on the basis of many years of research in the laboratory run by Arber, a specialist in  preventing cancer.

The first phase of CCOVID-19 is the flu-like viral infection that requires no special therapy, only supportive care. Phase two of the virus outbreak, which happens after five to seven days, can involve a rapid deterioration caused by an overreaction of the immune system, mainly in the lungs. Occurring in 5 to 7 percent of COVID patients, often in those with pre-existing risk factors, it is known as a cytokine storm. EXO-CD24 works by inhibiting that immune overreaction, which may be responsible for many of the deaths from the virus. Arber said that no drug has yet been proven to stop this from happening.

According to Dr. Shiran Shapira, director of Arber’s lab, EXO-CD24 is based on “exosomes, which are vesicles that are released from the cell membrane and used by the body for intercellular communication. We enrich the exosomes with a protein called CD24. This protein is expressed on the surface of the cell and is known as an important regulator of the immune system.”

The treatment is directed straight to the target organs — namely, the lungs. Other treatments either try to inhibit a specific cytokine or are aimed too broadly and threaten to cause severe side effects.

“In contrast, EXO-CD24 is given locally, has high efficacy, and does not cause any side effects,” Arber explained.

Out of the 30 patients with severe COVID-19 who were treated with the experimental drug in a Phase 1 clinical trial in Israel, 29 patients had “strong” improvement within two to three days. Most were discharged home within five days. The thirtieth patient also recovered after a longer hospitalization.

Arber added, “For efficacy we need to conduct the Phase 2/3 trials and compare it to placebo. We already have the Israeli regulatory approval and expect to start the enrollment of about 152 patients at the beginning of August.” 

According to Arber, with regulatory approval, the drug could be produced rapidly and inexpensively, supplying worldwide need within months.