Case Western Reserve University spinout Synapse Biomedical Inc. has received emergency use authorization from the U.S. FDA for its Transaeris diaphragm pacing system (DPS) device to prevent and treat ventilator-induced diaphragm dysfunction (VIDD). This condition occurs after mechanical ventilation, which weakens the unused diaphragm. A version of the minimally invasive device is already marketed by the Oberlin, Ohio-based startup for long-term use in spinal cord injury patients as Neurx.

Transaeris DPS has received a CE mark. The startup was already in the midst of a pilot study for the FDA in the VIDD indication prior to the onset of the novel coronavirus pandemic. By reducing the time necessary to re-strengthen the diaphragm with short periods off mechanical ventilation, Transaeris could help to reduce the time spent on mechanical ventilation by as much as one-quarter.

Diaphragm strength

“For this emergency use authorization, what we're trying to do is actually alleviate the burden on ventilators, ICU bed occupancy, and nursing staff in all patients that are on mechanical ventilators, so it's not just patients with COVID-19 but any patient that's in there for emergency or urgent use of an ICU bed and mechanical ventilation,” Synapse President and CEO Anthony Ignagni explained to BioWorld.

“For example, roughly half of the open-heart surgeries that are done nationally are still ongoing because they're urgent or emergency surgery,” he continued. “About 20% of those patients end up on mechanical ventilation for longer than 24 hours. So, in those patients we would use the Transaeris devices, for example, and shorten their time on the ventilator.”

The Transaeris system is a temporary percutaneous intramuscular diaphragm stimulator that is designed for patients on prolonged positive pressure mechanical ventilation. Up to two electrodes are inserted in each of the left and right hemi-diaphragms, these enable continuous neuromuscular electrical stimulation to the diaphragm throughout mechanical ventilation. The idea is to prevent, slow or reverse the atrophy of the unused diaphragm.

The system is intended to be used only once and then disposed of in order to prevent any infection transmission between ICU patients. Prior research indicates that this could reduce the mechanical ventilation burden by as much as 26%, since much of the final time spent on mechanical ventilation for patients who are improving is intermittent use that is specifically designed to strengthen the lungs sufficiently to function without support.

“If you think of the analogy of a broken arm or a broken leg, you break the bone and you put a cast on it so that bone can heal,” Ignagni said. “In the cast, the muscle that's supporting that bone atrophies. When you get the cast off and you'd have to recondition that arm or leg muscle to be able to function again.”

“For the lungs, your diaphragm starts to atrophy on mechanical ventilation,” he continued. “Once you're ready to come off, there have been multiple studies that have shown that 40% of the time that a patient is on a ventilator is spent actually trying to recondition that muscle. So, if you're on for ten days, for four of them your gas exchange is OK but the diaphragm isn’t good enough to support the lungs any longer.”

From pilot to market

Prior to the pandemic, Synapse had received the go-ahead from FDA for a 10-patient pilot trial of Transaeris in cardiac surgery patients. That pilot study was about one-quarter enrolled, but has since been put on hold. The startup expected to finish that study this year and then move on to a U.S. pivotal trial.

In Europe, Synapse has a CE mark for Transaeris and was in the process of putting together a marketing strategy there. So, the device is essentially still in pre-production mode, although Ignagni expects to be able to ramp up sufficiently to meet demand in the company’s existing 50,000 square foot facility that holds three clean rooms. The company is already hiring more workers.

He’s just not quite sure what that level of demand will be yet. With the April 15 announcement of the EUA from the FDA, Ignagni said he has received several inquiries already. Synapse expects to start with hospitals that it already has relationships with and are already familiar with its long-term Neurx product.

“Frankly, I don't know what the uptake is going to be,” said Ignagni. “We've gotten phone calls from around the world trying to obtain the device already. Before the pandemic hit, we had a broker trying to buy everything we had. We told him that that was an inappropriate use of our technology. So, we held off on that and want to make sure it gets into the hands of people who can effectively implement it. But we have the facilities here to ramp up significantly.”

Founded in 2002, Synapse first gained widespread attention when it was enrolling a clinical trial of Neurx in spinal cord injury. The late actor Christopher Reeve, who was left a quadriplegic after a horse-riding accident in 1995, requested to be a part of that trial. Once that news became public, that spinal cord injury study enrolled quite rapidly, Ignagni said.

But now the company whose mission started in spinal cord injury is hoping its technology can make a difference in combating the unfolding coronavirus pandemic. Currently, hospitalizations and ICU admissions have just recently started to peak in major U.S. metropolitan areas, while also circling the globe throughout Asia, the Middle East and Europe.

Major efforts to produce enough numbers of ventilators have struggled to meet demand, so any capability that could reduce that length of patient need for a ventilator and potentially free up needed equipment faster seems likely to be welcomed.

"Trauma and high-risk surgical and cardiac patients will continue to require ICU beds and ventilators that are also needed for COVID-19 patients," said Raymond Onders, chief of general surgery at the University Hospitals Cleveland Medical Center and professor at Case Western Reserve University School of Medicine. "In our case, utilizing Transaeris for high risk surgical and COVID-19 patients is protecting the supply chain of ventilators, ICU beds and clinical resources by reducing the time spent on mechanical ventilators by patients at risk or experiencing prolonged mechanical ventilation."

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