Cardiac arrest remains a serious cause of death and disability throughout the world. When the heart muscle is damaged severely, or a rhythm disturbance prevents blood flow, the brain suffers and suffers fast. Within a couple of minutes, neurons can be permanently injured once circulation stops. If this isn’t reversed quickly, lasting brain injury and even death are common outcomes. Recently, however, scientists have found an interesting inhalation therapy that might help protect brain cells post-cardiac arrest— Xenon gas therapy.
Xenon gas is a noble gas that has been traditionally used in lamps and headlights. But Xenon gas therapy can also be used to protect the brain based on prior research studies.
How Xenon Gas Therapy Prevents Brain Injury After Cardiac Arrest
To appreciate how Xenon gas therapy protects the brain after cardiac arrest, it helps to understand what normally occurs. Immediately after a cardiac arrest, specific receptors on brain neurons become activated. These receptors—called NMDA receptors—trigger calcium and other inflammatory particles to rush into the neurons, thus causing severe injury. This process adds insult to injury, so to speak, considering neurons are already being deprived of oxygen and glucose during a cardiac arrest.
Xenon gas therapy, however, stimulates receptors on these same brain cells and helps deactivate the NMDA receptors. If given soon enough, the inhalation therapy can prevent some of the injuries that might otherwise occur.
Based on prior research studies, Mallinckrodt and NPXe Limited are now advancing this inhalation therapy research to Phase III patient trials. If successful, favorable results are seen, Mallinckrodt and NPXe Limited will be granted fast-track status for possible drug treatment approval.
“We look forward to the upcoming start of the Phase 3 trial and learning more about this potential therapeutic option in a population of resuscitated cardiac arrest patients.” – Steven Romano, M.D., EVP and Chief Scientific Officer, Mallinckrodt Pharmaceuticals
Mallinckrodt and NPXe Limited’s Proposed Inhalation Therapy Phase III Trial
The inhalation therapy trial, which will be implemented in the U.S. and Europe, will involve over 70 medical centers and 1,400 patients. Xenon gas therapy will be administered through special devices provided by NPXe Limited. This plan will potentially include patients who are in hospitals and who are in transit in ambulances. In the study, half the patients will receive targeted temperature management, which is the currently approved treatment for cardiac arrest. The other half will receive Xenon gas therapy combined with temperature control. In this way, a good comparison can be made to determine just how beneficial Xenon gas therapy is for this patient population.
Mallinckrodt, a $1.68 billion pharmaceutical firm specializing in autoimmune and neurological conditions, partnered with NPXe Limited in this effort.
After NPXe Limited received regulatory approval for the Phase III trial, Mallinckrodt awarded NPXe Limited $5 million per their agreement. Mallinckrodt will have distribution rights for Xenon gas therapy in North America, Japan, and Australia—if they are given approval. NPXe Limited will provide both Xenon gas as well as the inhalation therapy devices required.
Fast Track Approval for Mallinckrodt’s and NPXe Limited’s Xenon Gas Trial
Prior research studies have shown that Xenon gas therapy has notable benefits for the brain following cardiac arrest. In a smaller, Phase II trial, cardiac arrest patients were administered Xenon gas therapy within 5 minutes of the arrest. High-level MRI brain scans showed patients receiving Xenon gas therapy had less damage in the deeper parts of the brain. The study did not look at functional outcomes long-term, and it only involved a small number of patients. But the findings were optimistic enough to prompt the current Mallinckrodt and NPXe Limited inhalation therapy trial.
Mallinckrodt and NPXe Limited have been given a Fast Track designation for the current study to expedite potential benefits. That means that ongoing monitoring of results will be performed in case clear inhalation therapy benefits are identified early.
“Receiving Fast Track designation expedites the review process and, if approved, inhaled xenon gas will help treat patients with an unmet medical need.” – Bill Burns, Chief Executive Officer, NeuroproteXeon
Study results are expected in 2020 at the latest, potentially offering new care options for cardiac arrest patients soon. If effective, Xenon gas therapy could notably improve neurologic outcomes that are, sadly, currently rather unsatisfactory for many cardiac arrest patients.