When it comes to the spinal cord stimulation market, Abbott Laboratories Inc.,Medtronic PLC and Boston Scientific Corp. are on top of the world, but one startup from Down Under hopes to "evoke" an entirely new response.
In contrast to existing spinal cord stimulation (SCS) systems that treat chronic pain by generating the same stimulation output through fixed (open-looped) technology, Evoke from Saluda Medical Pty. Ltd.. is a closed-loop system that can vary the intensity of every single pulse to match the patient’s preferred level.
"Evoke is the first and only fully implantable device to measure the response of the spinal cord to stimulation,” says Dan Bournstein, president of Saluda Medical.
This is a highly impressive feat, considering the device typically generates 60 pulses per second, or more than 5 million pulses a day.
Dan Brounstein, president of North America and senior VP of Saluda Medical, likens the information gleaned from Evoke to that of an electrocardiogram (EKG). But instead of providing insights into the heart, Evoke dives deep into the neurophysiology and pathophysiology of the spinal cord.
The cornerstone of the closed-loop technology is the evoked compound action potential (ECAP), which measures response of the spinal cord to stimulation.
"Evoke is the first and only fully implantable device to measure the response of the spinal cord to stimulation,” Brounstein told Medtech Insight. “This response is used in real-time by the programming technician to personalize therapy for each patient."
Evoke was first permanently implanted in a human in 2015. The implant is reversible and can be removed at any time. Saluda has completed multiple clinical trials of Evoke since 2009, comprising roughly 150 patients overall.
“The last two studies concluded that patients preferred closed-loop therapy to traditional open-loop therapy,” Brounstein said. “Furthermore, in our most recent study, at 12 months, more than 50% of subjects received greater than 80% pain relief, 53.8% of subjects reduced or eliminated their pain medications, and their overall disability and function improved significant.”
Results of the ongoing US pivotal study involving 134 patients are expected to be released next January.
That study is double-blinded, comparing closed-loop to open-loop SCS. “We hope the study will demonstrate superiority of closed-loop therapy to open-loop therapy,” Brounstein said. If all goes as planned, the company hopes to receive a CE mark for Evoke by the end of 2018, followed by PMA approval in the US by 2020.
For the US pivotal trial, Saluda is systematically collecting the ECAP so that differences between closed-loop stimulation and open-loop stimulation can be elucidated.
“Our goal is to use this information to develop a stimulation response curve similar to a pharmacological dose response curve, so that when SCS is chosen for patients with chronic pain, outcomes are more predictable and sustainable,” Brounstein noted.
Stimulation of the spinal cord excites the dorsal column fibers.
“When these fibers are excited, they generate action potentials which can be measured in voltage,” Brounstein explained. “That voltage is then used to control the loop, delivering more therapy at the patient’s therapeutic level and preventing overstimulation.”
The gold standard for conventional SCS is 50% of patients achieving 50% pain relief, according to Brounstein, which is "not bad, considering the alternative," he said.
"But we strive to do better for patients. Our objective is to provide outcomes beyond simply pain relief. We want to improve all aspects of a patient’s life," he said.
In the US, there are about five million people with chronic, intractable neuropathic pain of the trunk and/or limbs who could potentially benefit from Evoke, representing a market opportunity of $100bn.
“In light of the opioid crisis, physicians are searching for alternatives to expensive and addictive pain medications,” Brounstein said. “However, currently, the SCS market has only about a 5% to 10% penetration.”
Saluda was started in 2013 as a spin-out from the National Information and Communications Technology Australia (NICTA) Research Centre of Excellence. Two years prior at NICTA, future Saluda founder and CEO John Parker and others began developing the closed-loop SCS system.
“We were interested in recording the activity of nerves, which is the hardest to detect for SCS because the electrodes are a very long distance from the spinal cord in a completely dynamic environment,” said Parker, who helped lead the Implant Systems Team at NICTA from 2009 to 2013. Prior to that, he was the chief technology officer and an executive director at Cochlear Limited (which makes cochlear implants for the profoundly hearing impaired and deaf) from 1993 to 2007.
SALUDA MEDICAL EVOKE SCS SYSTEM, SOURCE: SALUDA MEDICAL
Brounstein, meanwhile, joined Saluda in 2015 after serving as VP of marketing and clinical operations at Spinal Modulation Inc. (acquired by St. Jude Medical Inc.) for seven years prior.
Looking back, Parker said, recording the ECAP proved the most challenging part of the project.
“We needed to build a device that could measure tiny voltages produced by the nerve fibers immediately after the stimulus occurred,” Parker said. “But there is a lot of artifact that remains from stimulation. In fact, sometimes the artifact drowns out your capacity to record.”
As a result, there is a tremendous amount of signal processing that takes place inside Saluda’s implant. The algorithm that tracks the response from the nerve was also difficult to develop.
“These challenges took years of pain-staking lab work, including careful modeling, understanding the physics and building multiple iterations of amplifiers,” said Parker.
Saluda has 12 issued patents and 65 patent families pending and does not share any royalties and/or revenues with another entity.
Typically, the patient can test-drive the therapy for roughly one week prior to receiving the implant.
An anesthesia pain specialist or a neurosurgeon implants Evoke in an outpatient procedure that is normally completed in less than one hour. The implant’s lead is first introduced into the epidural space with a small needle, similar to an epidural anesthesia technique. The lead is then tunneled to a pocket in the buttock or abdomen, where the implant is secured.
After implanting, a technician programs Evoke to the patient’s preferred level and then instructs the patient on how to use a wireless remote control.
“During the first three months, patients often adjust settings slightly, either up or down, for better pain relief,” Parker said. “But after that time period, patients can stop using the remote control altogether.”
Saluda has raised a total of $70 million through four rounds of financing: $7 million that closed in 2013, funded by private high-net-worth individuals and Australian government grants; $7 million in 2015, led by Biosciences Managers Pty Limited; a $16 million Series A preferred round in 2016, comprised of existing shareholders and Medtronic; and a Series B preferred round that raised $40 million and closed in 2017, led by Action Potential Venture Capital (APVC).
Meanwhile, one sizable investor, Cochlear Limited, is evaluating Saluda's recording technology for use in hearing. But Saluda is keeping all options open for an exit strategy.
The company has also conducted human studies for three other neuromodulation applications: deep brain stimulation (DBS) for Parkinson’s disease; sacral nerve stimulation for bowel and bladder incontinence; and peripheral nerve stimulation.