RedHill Biopharma Ltd. is hoping a new drug it is developing will become a “game changer” in the global battle against COVID-19, Gilead Raday, the chief operating officer of the Israeli biopharmaceutical firm said in an interview.
The firm, whose main focus has been on gastrointestinal diseases, has developed a new molecule — a chemical entity that boosts anti-inflammatory and anti-viral activity in cells, and was found in 2016 to be effective in vitro experiments against the Ebola virus. As the Ebola virus subsided, the firm halted development of the molecule.
Now, with the novel coronavirus wreaking havoc globally with almost 24 million infected people worldwide and more than 800,000 deaths, the Tel Aviv-based firm founded by two kibbutz members hopes the drug it’s developing, Opaganib, will prove to be effective in treating the deadly illness caused by the virus.
RedHill believes the molecule “could be very effective as an antiviral and as an anti-inflammatory, protecting the lungs. The dual mechanism of action is something that was very promising,” Raday said.
Opaganib is currently being developed to treat severe, hospitalized patients that are not intubated, he said. The drug is administered orally.
Earlier this month the company said that it got a nod from the Mexican Federal Committee for the Protection against Sanitary Risks to start a Phase II/III study evaluating the drug in patients hospitalized with severe SARS-CoV-2 infection, caused by COVID-19, and pneumonia, who require hospitalization and treatment with supplemental oxygen.
Subjects will be randomized to receive either Opaganib or a placebo, along with standard-of-care therapy. The main aim of the study is to evaluate the effectiveness of the drug and the proportion of patients that still require intubation and mechanical ventilation by day 14.
The Phase II/III study has now been approved in Mexico, the UK, and Russia and is under review in Italy, Brazil and additional countries. Further expansion of the study to other countries is also planned, said Raday.
The company has also already started enrolling patients for an ongoing, albeit smaller, Phase II study in the US, and if the two studies are successful, then the company hopes to apply for authorization for emergency use of the drug as early as the fourth quarter of this year.
“We plan to enroll 270 patients across these countries,” Raday said in the interview, referring to the larger, international study. The idea is to develop a drug that will be a therapy for the illness, not a vaccine to prevent it, he explained.
Pre-clinical data has shown that the drug has both anti-inflammatory and anti-viral properties, with the potential to reduce lung inflammation disorders, such as pneumonia, and mitigate pulmonary fibrotic damage, the company said.
Compassionate and experimental use of the drug in Israel has had “encouraging results,” Raday said. Indeed, the drug was administered to seven patients at an Israeli hospital who were “at high risk to die,” he said. Compassionate use is when medical personnel treat patients with experimental drugs outside of clinical trials, under special circumstances, and with the approval of medical authorities.
All patients in the Opaganib-treated group were discharged from hospital without requiring mechanical ventilation, whereas 33% of the matched control group required mechanical ventilation, the company said in a statement earlier this month.
Patients treated with the drug were also weaned earlier from a high-flow nasal cannula that is used to treat patients with acute respiratory failure — the time was cut to 10 days in the Opaganib-treated group, as compared to 15 days in the matched case-control group.
“On top of clinical outcome, we had very good results from inflammatory and other markers,” said Raday. The lymphocyte count, for example — a type of white blood cell — was “very significantly” higher in the treated group, as opposed to the non-treated group, which is a good indication of the viral infection “being overcome,” he said. Markers indicating general inflammation also declined faster in the treated group.
Raday explained that the drug targets a unique enzyme called the sphingosine kinase-2 (SK2) and inhibits its activity. This inhibition reduces both inflammation levels but also halts the virus from replicating.
“When it is out of balance, this enzyme potentially increases cytokines and inflammation, and by inhibiting it, you create a normalization of the levels of some of these cytokines – it brings them back to normal,” said Raday.
Research has shown that the so called “cytokine storm” is an uncontrolled over-production of inflammation markers which, in turn, cause an aberrant systemic inflammatory response, a major factor in the occurrence of Acute Respiratory Distress Syndrome which is a result of the COVID-19 infection.
In addition, after viruses infect a cell, they seek to replicate, but cannot do so without taking the cell’s mechanism “hostage,” Raday explained. The SK2 enzyme which Opaganib inhibits, “is a component that is required for the replication of the virus in the cell,” and by inhibiting it, replication cannot happen, he said.
Raday added that current drugs being used to treat COVID-19 patients — including Remdevisir and Dexamethasone, a corticosteroid used for its anti-inflammatory and immunosuppressant effects, have been found to be effective in treating the deadly illness, but there are “unfortunately” not game-changing treatments in the market at the moment.
RedHill is now going full steam ahead in trying to enroll patients for its international Phase II/III study, and hopes to have results of the study in the fourth quarter of this year.
“If we see similar results to what we saw in the compassionate use, that would be really outstanding results, which should support emergency use authorization,” of the drug, said Raday.
The firm is already preparing for the manufacture and commercial distribution by the end of the year.
“If we give this to patients who are hospitalized and on oxygen and only a minor percentage of them progress to require mechanical ventilation, and they just become better within a few days, then it becomes a totally different profile of the disease — a manageable disease,” said Raday. The impact of such a drug “goes beyond patients and their lives,” he added, as it could help avoid future global shutdowns in a bid to curb the spread of the virus. “That makes everything else less scary.”
The shares of the company traded on the Nasdaq have advanced 11 percent in the past 12 months, leading it to a valuation of $284 million.