BARDA, Enalare Therapeutics to reformulate respiratory stimulant for emergency treatment of opioid-induced respiratory depression

The Biomedical Advanced Research and Development Authority (BARDA) and Enalare Therapeutics partnered this week to reformulate the agnostic respiratory stimulant ENA-001 into an intramuscular, emergency treatment for opioid-induced respiratory depression (OIRD).

The action is being undertaken through the Repurposing Drugs in Response to Chemical Threats (ReDIRECT) program, and as such, BARDA will provide funding for the reformulation effort. The reformulated drug will undergo preclinical pharmacokinetic testing to guarantee its efficacy.

Even in its present state, ENA-001 is a new chemical entity. Researchers are interested in its potential usefulness for treating OIRD and other types of respiratory depression, a condition in which slow and ineffective breathing can lead to low levels of oxygen and high levels of CO2. It is not uncommon after the use of opioid analgesics, and, left untreated, the condition could become life-threatening through respiratory failure. ENA-001 has potential as a rapid medical countermeasure, both in mass casualty situations and everyday overdoses.

Another formulation of ENA-0001 is intravenous, and that version is currently undergoing clinical trials and evaluation as a treatment for drug overdose and postoperative respiratory depression. Separate, early clinical studies are evaluating the drug’s potential for treating silent hypoxemia among COVID-19 patients and patients being weaned off of mechanical ventilation.

The diversity of hopes for the drug rest on its agnostic nature. It acts through the carotid body’s peripheral chemoreceptors and is not specific to opioids, meaning it could be particularly useful against combined drug overdoses.

Currently, treatment options for opioid overdoses are limited to a class of drugs that have proven incapable of keeping up with the extended half-life of highly potent synthetic opioids like illicit fentanyl, which have proven devastating to millions in the U.S. Researchers have been searching for new treatments with different mechanisms to overcome existing limitations. Of particular interest are those capable of evading withdrawal symptoms, which current options often suffer.