If you were superstitious, what happened next might have looked like an omen. The word “electroceutical” already belonged to someone else—a company called Ivivi Technologies had trademarked it in 2008. “I am fairly certain we sent them a letter soon after they started that campaign, to alert them of our trademark,” says Sean Hagberg, a cofounder and then chief science officer at the company. Today neither GSK nor SetPoint can officially call its tech “electroceuticals,” and both refer to the implants they are developing as “bioelectronic medicine.” However, this umbrella term encompasses a wide range of other interventions, some quite well established, including brain implants, spine implants, hypoglossal nerve stimulation for sleep apnea (which targets a motor nerve running through the vagus), and other peripheral-nervous-system implants, including those for people with severe gastric disorders.
MIKE DENORA VIA WIKIPEDIA
The next problem appeared in short order: how to target the correct nerve. The vagus nerve has roughly 100,000 fibers packed tightly within it, says Kip Ludwig, who was then with the US National Institutes of Health and now co-directs the Wisconsin Institute for Translational Neuroengineering at the University of Wisconsin, Madison. These myriad fibers connect to many different organs, including the larynx and lower airways, and electrical fields are not precise enough to hit a single one without hitting many of its neighbors (as Ludwig puts it, “electric fields [are] really promiscuous”). This explains why a wholesale zap of the entire bundle had long been associated with unpredictable “on-target effects” and unpleasant “off-target effects,” which is another way of saying it didn’t always work and could carry side effects that ranged from the irritating, like a chronic cough, to the life-altering, including headaches and a shortness of breath that is better described as air hunger. Singling out the fibers that led to the particular organ you were after was hard for another reason, too: the existing maps of the human peripheral nervous system were old and quite limited. Such a low-resolution road map wouldn’t be sufficient to get a signal from the highway all the way to a destination.
In 2014, to remedy this and generally advance the field of peripheral nerve stimulation, the NIH announced a research initiative known as SPARC—Stimulating Peripheral Activity to Relieve Conditions—with the aim of pouring $248 million into research on new ways to exploit the nervous system’s electrical pathways for medicine. “My job,” says Gene Civillico, who managed the program until 2021, “was to do a program related to electroceuticals that used the NIH policy options that were available to us to try to make something catalytic happen.” The idea was to make neural anatomical maps and sort out the consequences of following various paths. After the organs were mapped, Civillico says, the next step was to figure out which nerve circuit would stimulate them, and settle on an access point—“And the access point should be the vagus nerve, because that’s where the most interest is.”
Two years later, as SPARC began to distribute its funds, companies moved forward with plans for the first generation of implants. GSK teamed up with Verily (formerly Google Life Sciences) on a $715 million research initiative they called Galvani Bioelectronics, with Famm at its helm as president. SetPoint, which had relocated to Valencia, California, moved to an expanded location, a campus that had once housed a secret Lockheed R&D facility.
How it’s going
Ten years after electroceuticals entered (and then quickly departed) the lexicon, the SPARC program has yielded important information about the electrical particulars of the peripheral nervous system. Its maps have illuminated nodes that are both surgically attractive and medically relevant. It has funded a global constellation of academic researchers. But its insights will be useful for the next generation of implants, not those in trials today.
Today’s implants, from SetPoint and Galvani, will be in the news later this year. Though SetPoint estimates that an extended study of its phase III clinical trial will conclude in 2027, the primary outcomes will be released this summer, says Ankit Shah, a marketing VP at SetPoint. And while Galvani’s trial will conclude in 2029, Famm says, the company is “coming to an exciting point” and will publish patient data later in 2024.
The results could be interpreted as a referendum on the two companies’ different approaches. Both devices treat rheumatoid arthritis, and both target the immune system via the peripheral nervous system, but that’s where the similarities end. SetPoint’s device uses a clamshell design that cuffs around the vagus nerve at the neck. It stimulates for just one minute, once per day. SetPoint representatives say they have never seen the sorts of side effects that have resulted from using such stimulators to treat epilepsy. But if anyone did experience those described by other researchers—even vomiting and headaches—they might be tolerable if they only lasted a minute.