FiveLiters Demonstrates Progress in Stopping the Bleeding

by JoJo Platt, senior contributing editor

December 2024 issue, BioElectRx Business Report

While the 21st century is well underway, it seems almost comical that our greatest methods for controlling bleeding are to apply pressure, apply pads, and elevate the affected area above the heart—if possible. The tourniquet, which dates back at least to Morel’s use in the mid sixteenth century, can be exceptionally effective for limbs, but not a great option for visceral wounds. These tried and sometimes true techniques unquestionably save lives in wounded individuals but offer no relief for people living with bleeding disorders. Whether inherited acquired, bleeding disorders affect more than 3 million people in the U.S. according to the latest numbers from the CDC.

The U.S. government and the military have a vested interest in developing tools and techniques to control bleeding in both injury and illness. In the early 2000’s DARPA backed one such effort that came to be known as “The Neural Tourniquet.” Chris Czura, while at the Feinstein Institutes for Medical Research, performed the early animal model work that may lead to the biggest improvement in treatment options for controlling bleeding by injury or illness. The use of vagus nerve stimulation to prime blood platelets would spend nearly two decades in development before landing a commercial home as FiveLiters, a part of the Spark Biomedical family.

Spark Biomedical has successfully launched the Sparrow Ascent, an FDA-cleared, non-addictive, non-invasive, wearable treatment technology for the relief of opioid withdrawal symptoms. The device uses transcutaneous auricular neurostimulation to release endorphins to fill the opioid receptors followed by a flow of dopamine, which can help with pain-relief.

FiveLiters is also using the proprietary tAN technique albeit at different stimulation parameters to “prime platelets” allowing for much better and stronger clotting. Previous animal studies conducted by Czura, Jared Huston, and others demonstrate tANs ability to cut shed blood time and shed blood volume by 50 percent and even offers prophylactic benefit meaning you can stimulate before an injury and still obtain blood-saving results. This makes the technology potentially ideal for warfighters in advance of mission deployment and even routine or emergency surgery.

How exactly does tAN work? Czura explained that the electrical stimulation applied to the nerves in the ear, including the vagus nerve, sends a signal to the spleen. Acetylcholine then increases calcium concentrations in platelets resulting in a priming effect. The primed platelets are not activated but are inherently more sensitive to pro-coagulant triggers.

The newest data to come out of FiveLiters is from their pilot study which looked at the device’s ability to affect heavy menstrual bleeding particularly in women with Von Willebrand disease. Researchers looked at more than 20 healthy subjects to confirm the mechanism and demonstrate that tAN upregulates platelet receptors and improves clot firmness. The pilot study focused on heavy menstrual bleeding in both VWD and non-VWD women. Participants were monitored for one month without stimulation. In the second month, women were asked to stimulate twice each day during menstruation.

In addition to the outstanding on-target effects of a greater than 50% reduction in menstrual blood loss compared to baseline and roughly a 25% reduction in the duration of menstruation, subjects reported significant improvements in quality of life scores. Notably, women experienced tremendous improvements in reduced cramps, nausea, irritability, increased physical functioning, energy levels, and emotional well-being. Specifically, patients reported spending roughly 40% less time in bed and reductions in cramp severity and nausea severity by 54% and 50% respectively.

If such dramatic results were seen in a drug trial, one might be quick to ask about the side effects. While the pilot sample size is relatively small at under 50 participants, the feedback is inversely huge. One subject reported challenges related to device fit but noted her ears were “on the small side” and another mentioned slight redness at the stimulation site while yet another trial participant exalted, “best period ever!”

Next steps: FiveLiters will launch a pivotal trial in early 2025 and expects to publish data from the pilot study in Q1 ’25. If you have any bit of imagination, you’re already calculating the different potential markets for the Neural Tourniquet and so has FiveLiters. In an interview with CEO Daniel Powell and CSO Navid Khodaparast, BBR learned that the opportunities are indeed vast, and several studies are already underway but the team is laser-focused on giving the world a new way to stop the bleeding.