In a controlled laboratory test, Eagle Pharmaceuticals’ malignant hyperthermia treatment Ryanodex (dantrolene sodium) inhibited the growth of SARS-CoV-2, the virus causing the COVID-19 pandemic. Now the company hopes to launch a clinical trial testing the efficacy of the drug in patients.
In the in vitro tests, Ryanodex demonstrated antiviral activity and a lack of cytotoxicity. Two days after dosing, the in vitro results showed an absence of cytopathic effects in the infected cells. This morning, New Jersey-based Eagle Pharmaceutical submitted its Investigational New Drug Application to the U.S. Food and Drug Administration to launch a Phase II trial in partnership with Hackensack University Medical Center to evaluate the efficacy of Ryanodex in patients infected with SARS-CoV-2. The company said it has been in contact with the FDA’s Coronavirus Treatment Acceleration Program to request a potential expedited review of the IND application and aims to begin the clinical trial as soon as possible.
Ryanodex acts by modulating free intracellular calcium levels to restore calcium homeostatic balance inside cells. Eagle is exploring the relationship between viral infection and the regulation of calcium levels inside cells. Depending on the virus type, an altered intracellular calcium balance may enhance virus entry, replication and release, the company said. As a result, intracellular calcium levels may be an important factor in viral-host interactions and viral infections, Eagle noted in its announcement.
Eagle said the Phase II trial will use the World Health Organization Ordinal Scale of Severity, the Sequential Organ Failure Assessment and other relevant clinical measurements will be used as efficacy endpoints. The trial will enroll approximately 60 adult COVID-19 patients with confirmed SARS-CoV-2 infection. The company anticipates results from the trial in May if the FDA gives it the green light.
“The results of Eagle Pharmaceuticals’ virus neutralization assay demonstrated a lack of viral growth in Ryanodex-treated cells compared to those not treated with Ryanodex. This outcome suggests that Ryanodex may have antiviral activity against SARS-CoV-2, which we believe represents a novel approach to impeding the virus lifecycle by modulating free intracellular calcium levels of host cells,” Adrian Hepner, chief medical officer of Eagle Pharmaceuticals said in a statement. “We now plan to conduct a clinical trial in partnership with Hackensack University Medical Center to evaluate the efficacy and safety of RYANODEX as a potential treatment for patients hospitalized with COVID-19.”
In its announcement this morning, Eagle said it is increasing production of Ryanodex, which was initially approved by the FDA in 2014 for the life-threatening malignant hyperthermia, in advance of clinical trials and to potentially shorten the supply chain lead time if necessary. To support this, Eagle forged a strategic manufacturing partnership with Amneal Pharmaceuticals, Inc. Eagle is also working with its existing manufacturing partner, Durham, N.C.-based Alcami Corporation to increase the production of the drug.