Onward and Upward in Treating Spinal Cord Injury

Spinal cord injury (SCI) is a major unmet clinical need—and as of yet, there’s no cure. About 7 million people worldwide suffer from SCI, with more than 650,000 in the United States and Europe alone. Quality of life with SCI can include such woes as paralysis and loss of sensation, issues with blood pressure control and trunk stability, increased potential for infection, incontinence, and loss of sexual function. Daily living activities almost always require assistance.

Onward Medical was formed in 2014 by neuroscience researchers at the Swiss Federal Institute of Technology (EPFL) with the goal of improving quality of life after SCI. The company now is headquartered at the High Tech Campus in Eindhoven, The Netherlands, with offices in Lausanne, Switzerland, and a growing U.S. team based in Boston.

The company’s ARC therapy can be delivered by external (ARC-EX) or implantable (ARC-IM) systems. It delivers targeted, programmed spinal cord stimulation to restore movement and other functions in people with SCI. ARC-EX consists of a stimulator and wireless programmer. ARC-IM consists of an implantable pulse generator and lead placed near the spinal cord; it is controlled by wearable components and a smartwatch.

The ARC-EX system first received breakthrough device status from the U.S. Food and Drug Administration (FDA) in 2017 for improved upper limb function in SCI patients. ARC-IM gained breakthrough status in 2020 to restore leg motor function in 2021 to normalize blood pressure and provide trunk stability, and in 2022 for bladder control.

The company completed enrollment for its Up-LIFT pivotal trial of ARC-EX in December 2021. The first large-scale pivotal trial of its kind, UpLIFT evaluated ARC therapy to restore hand and arm function in people with SCI. Sixty-five subjects were enrolled at 14 sites in the U.S., Canada, the U.K., and The Netherlands.

“The study reached its enrollment objective in under 12 months despite lock-downs, travel restrictions, and other COVID-related challenges,” Onward CEO Dave Marver said. “This milestone underscores the SCI community’s enthusiasm for this promising therapy.”

In September 2022, the company reported that Up-LIFT achieved its primary endpoint of improving upper extremity strength and function. Patients completed an average 50 training sessions over a period of about four months. The pivotal study also showed a 72% responder rate.

A month later, Onward reported the results of its LIFT Home study evaluating ARC-EX use to treat SCI at home. All patients finished the study with no adverse events. Ninety-seven percent of the therapy sessions were successfully completed, which supported the feasibility of home use.

ARC-EX was awarded FDA breakthrough status in February 2023 for bladder control, spasticity alleviation, and blood pressure regulation in SCI patients. This raised the number of breakthrough device designations to eight for the platform.

The first successful human implant of the ARC-IM stimulator to restore upper extremity function after SCI occurred in May 2023. It marked the first time the ARC-IM targeted, programmed spinal cord therapy was used to restore movement and function in this area of the body.

In January 2024, the company began a feasibility study called HemON NL at Sint Maartenskliniek in Nijmegen, The Netherlands. It is evaluating ARC-IM therapy for hemodynamic instability after SCI and preparing Onward to start its Empower BP global pivotal trial, which hopes to provide evidence for submission to the FDA for premarket approval.

The company presented clinical experience, results, and programming strategies during the North American Neuromodulation Society meeting in January as well.

“We are preparing to submit a De Novo application for ARC-EX Therapy to FDA in the near future, leveraging the positive clinical results from the Up-LIFT pivotal study,” Marver said.

At the end of February, Onward was awarded another breakthrough nod—its tenth so far—for the ARC-BCI (brain-computer interface). The implanted BCI works in tandem with ARC-IM therapy to restore thought-driven mobility after SCI—an implanted BCI records brain activity and captures signals that indicate the person’s potential to move. ARC-BCI then uses artificial intelligence to decode the signals and translate them into instructions for ARC-IM. ARC-IM then converts the instructions into stimulation of the injured spinal cord.

Essentially, it creates a “digital bridge” to restore communication between the brain and body, allowing thought-driven movement after paralysis.

The latest breakthrough status was granted based on clinical data from two feasibility studies. The latest award provides the company with priority FDA review. Onward also plans to explore other potential indications for ARC therapy including reduced spasticity, improved sexual function and bowel control, BCI, Parkinson’s mobility, and gait.