Saluda Medical Reports Final Long-Term Results out to 24 Months from Avalon Study and Results at 12 Months from U.S. Evoke Pivotal Study

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Saluda Medical

27 Jan, 2020, 13:58 GMT

Key Findings Highlighted in Multiple Presentations, Including Best Clinical Abstract, at NANS 2020

HARROGATE, England, Jan. 27, 2020 /PRNewswire/ -- Saluda Medical Pty Limited ("Saluda Medical") today announced that new data, from multiple studies evaluating the company's Evoke® ECAP-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) System for the treatment of chronic pain, were presented in a series of oral and poster presentations, including Best Clinical Abstract, during the North American Neuromodulation Society (NANS) 23rd Annual Meeting, held January 23-26, 2020 in Las Vegas, Nevada, United States.

The data included final results out to 24 months from the Australian Avalon study and results at 12 months from the U.S. Evoke Pivotal Study.

John Parker, CEO of Saluda Medical, commented, "As we expand commercialization in Europe, we believe the collective results from these studies, along with the aggregate real-world experience in the first European centers, provide substantial evidence that supports the advantage of the Evoke therapy.  As the first and only ECAP-controlled, closed-loop SCS system, Evoke enables the ability to objectively define the therapeutic window for each patient, which leads to greater levels of spinal cord activation and more time within this therapeutic window over the long term, enabling patients to achieve better pain relief, including secondary outcomes such as improved sleep quality, reduced disability, and reduced opioid use. We believe these results substantially advance the field of neuromodulation."

Oral Presentations

Avalon Study: Long-Term Impact of ECAP-Controlled Closed-Loop SCS on Pain, Patient Wellbeing and Clinical Practice

  • Outcome measures from the Avalon multicenter study in Australia demonstrate large, clinically important improvements that are sustained or improved out to 24 months.
  • Providing consistent spinal cord activation and stimulation within the therapeutic window may be the mechanism for sustained efficacy.
  • The sustained clinical benefit coupled with low programming burden in the long-term, suggests closed-loop SCS is an important tool for treating chronic neuropathic pain.
  • Key results:
    • Patients' responder rates improved over time from 12 months to 24 months as evidenced by 53.5% of subjects achieving ≥80% pain relief at 12 months and 68.4% of patients achieving ≥80% pain relief at 24 months.
    • At 12 months, 68.8% of subjects reduced opioid intake. At 24 months, the percent of subjects who reduced opioid intake increased to 82.8%.

ECAP-Controlled Closed-Loop SCS:  Double-Blind, Randomized Trial for the Treatment of Chronic Pain: 12-month Outcomes

  • The randomized, double-blind study design of the U.S. Evoke Pivotal Study was developed to preserve objectivity and minimize bias. The randomization produced well-matched treatment groups.
  • ECAP-controlled closed-loop SCS provided statistically superior pain relief.
  • The time spent in the therapeutic range was almost double and the most frequent spinal cord activation level was six times greater with closed-loop compared to open-loop.
  • Closed-loop improved on all patient reported outcome measures (sleep quality, physical/emotional functioning, and health-related quality of life) and opioid reduction to a greater degree than open-loop.
  • Greater rates of improvement in subjective outcomes coincided with higher, more consistent spinal cord activation within patients' therapeutic range of activation in the closed-loop group. This suggests that the level and consistency of spinal cord activation (i.e., lack of variability in stimulation reaching the target), regardless of algorithm, may be mechanistically important for outcomes with SCS.
  • Note: Full results of the U.S. Evoke Pivotal Study were recently published in The Lancet Neurology.

"High Responders" to Neurostimulation Show Greater Clinical & Overall Meaningful Response in Patient Reported Outcomes

  • In the U.S. Evoke Pivotal Study, high responders who had greater analgesic benefit compared to responders (≥80% vs. ≥50% to <80% VAS reduction in overall back and leg pain), also demonstrated greater, more clinically meaningful benefits in physical functioning, emotional functioning, sleep quality, and quality of life. This analysis demonstrates the importance of assessing outcomes using a number of measures to better interpret the treatment effect and full benefit to the patient.
  • The incidence of ≥80% reduction in VAS overall pain was statistically superior for closed-loop (55.9%) compared to open-loop SCS (37.3%) at 12 months.
  • Key results:
    • 48.3% of high responders improved to become minimally disabled (vs. 21.9% of responders).
    • With sleep, 40.4% of high responders converted from poor to good sleep quality (vs. 16.1% of responders).
  • Utilization of objective neurophysiological measurements to confirm the intended target of therapy in programming and closed-loop SCS to maintain spinal cord activation at therapeutic levels may result in a greater probability of a high response (high responders spent a greater percentage of time in the therapeutic window).

Long-Term Robustness of Evoked Compound Action Potentials (ECAPs) as a Physiological Monitoring Tool

  • Results from the U.S. Evoke Pivotal Study establish that ECAP recordings are a robust neurophysiological monitoring tool that can be utilized long-term.
  • ECAPs and their derivatives are a valuable tool to measure neural health and SCS therapy over time.
  • Objective measurements using ECAPs are stable over time indicating that the population of activated fibers, the ability to excite them, and their response to stimulation are consistent over time.
  • However, although not statistically significant, it was observed that ECAP amplitude based on patient perception level changed over time in the open-loop group.

Therapeutic Levels and Variability of Spinal Cord Activation: Closed-Loop v. Open-Loop Spinal Cord Stimulation (SCS)

  • In the U.S. Evoke Pivotal Study, data collected for comparison of in-clinic versus out-of-clinic ECAP amplitudes for a patient who elected to try both open-loop and closed-loop stimulation revealed that usage patterns shift based on whether the patient used open-loop SCS or closed-loop SCS.
  • In open-loop SCS, high spinal cord activation variability in-clinic resulted in more stimulation near and above Maximum, potentially inducing more side-effects. Presumably, out-of-clinic, open-loop SCS patients decrease their stimulation amplitude to avoid these over-stimulations, and as such their mode spinal cord activation is only 1/6th of closed-loop SCS patients.
  • Closed-loop SCS patients use the device closer to in-clinic levels, with the closed-loop SCS patients experiencing less variability, higher spinal cord activation levels, and reporting better pain outcomes.

Defining the Therapeutic Window for Spinal Cord Stimulation using Evoked Compound Action Potential (ECAP) Recordings

  • Secondary results from the Avalon and Evoke studies demonstrate that without a measure of spinal cord activation (e.g., ECAPs), therapeutic window can only be based on perception of stimulation intensity or current, which are highly variable depending on patient posture changes and movement. However, therapeutic window can be individually defined by ECAP amplitudes, an objective measure of SC activation in all postures.
  • Monitoring spinal cord activation within the therapeutic window over time could provide insights into the effectiveness of, and potential improvements to, SCS therapy.
  • Key results:
    • In the U.S. Evoke Pivotal Study, closed-loop patients had significantly more stimuli in the therapeutic window (median 95.2% closed-loop vs. 47.9% open-loop at 12 months) with spinal cord activation closer to the comfort level.
    • Data from the Avalon study showed similar percentages of stimuli in the therapeutic window for patients with closed-loop long-term (median percent stimuli were 96.7% at 3 months and 84.9% at 12 months), showing the therapy can be maintained within the therapeutic window over time.

Sleep Quality Improvements Observed in the Evoke Study of ECAP Measurement and ECAP-Controlled Closed-Loop SCS

  • In the U.S. Evoke Pivotal Study, marked improvements in sleep quality were observed in both closed-loop and open-loop groups, with greater improvement trending in the closed-loop group.
  • ECAP measurement may contribute to improved outcomes by confirming the activation of the dorsal column and thus pain inhibition. The addition of closed-loop to adjust activation levels at the spinal cord might avoid over-activation of sleep-related neuronal activities, and in-turn, lead to improved sleep outcomes.
  • Key results:
    • At baseline, only 1.6% of closed-loop and 3.2% of open-loop patients reported good sleep quality (PSQI Total Score ≤ 5).
    • At 3 months, 32.8% of closed-loop patients and 28.3% of open-loop patients, reported good sleep quality, and it was maintained at 12-months (30.9% and 27.1%, respectively).
    • At 3 months, 75.9% of closed-loop patients reported a clinically significant change (reduction in PSQI Total Score from baseline ≥ 3) versus 66.0% of open-loop patients (p=0.297). Although not statistically significant, this trend was maintained at 12 months, with 76.4% of closed- patients and 62.5% of open-loop patients (p=0.138) experiencing a reduction in PSQI Total Score ≥ 3 points.
    • Mean duration of sleep scores went from approximately 2 at baseline to 1 at 12-months follow-up, which translates to up to 2 additional hours of sleep per night.

Poster Presentations

Understanding the Effect of Titrating Medication with SCS Using Evoked Compound Action Potentials (ECAPs)

  • Previous work from the U.S. Evoke pivotal study has presented a case study on the effect of medication out to and beyond 12-months post-implant of the Evoke system; this poster presents data for 2 additional subjects.
  • Findings shows that the therapeutic window decreased with decreased opioid/ anticonvulsant dose (and vice versa).
  • ECAP amplitude may be used to titrate and optimize dosing of anticonvulsants and opioids.
  • An SCS system, capable of measuring ECAP amplitude and maintaining it at a preferred level, may result in improved long-term outcomes.
  • A more controlled study is required in order to determine how much, if at all, neural excitability has been affected, and to understand the effect of medication better in general.

Evoked Compound Action Potentials (ECAPs): Helping to understand Spinal Cord Stimulation (SCS)

  • ECAP recording has many applications, one of which is ECAP-controlled closed-loop SCS.
  • ECAP recording continues to provide many insights into the effects of SCS, some of which have already helped improve understanding of SCS, including:
    • the types of fibers stimulated;
    • providing an objective measure of neural activation;
    • enabling objective lead placement;
    • more objective programming
    • monitoring of SCS usage over time; and
    • monitoring potential changes in neural sensitivity and conduction.

About Saluda Medical

Saluda Medical is a global medical device company focused on patient outcomes, science, and engineering to transform the neuromodulation industry with a platform of closed-loop technologies based on the evoked compound action potential (ECAP). Saluda's first device, Evoke®, is the first ECAP-Controlled, Closed-Loop Spinal Cord Stimulation (SCS) System. Evoke measures the spinal cord's response to stimulation (ECAP), adjusts on every pulse to optimize activation within the patient's therapeutic window, and maintains long-term results through ECAP control as demonstrated in the Avalon Study and Evoke Study. In the EU, Evoke is CE Marked and commercially available. In the U.S., Evoke is currently under investigation through the first double-blinded, randomized, controlled U.S. pivotal study in SCS and is not commercially available.

Saluda Medical is a privately-held company with headquarters in Artarmon, New South Wales, Australia and offices in Bloomington, MN, USA and Harrogate, UK. To learn more, visit www.saludamedical.com and connect with us on LinkedIn at www.linkedin.com/company/saluda-medical/.

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