Saluda Medical Pty. Ltd. has caught the attention of yet another big name in the health care industry, with the closing of a Aus$53m ($40m) Series D financing round led by new investor Action Potential Venture Capital (APVC) – the fund set up in 2013 by pharma giant GlaxoSmithKline PLC to invest exclusively in bioelectronic medicines. APVC was joined by Saluda's existing shareholders, including medtech's biggest player Medtronic.
The funds will be used primarily to support the Australian firm's clinical activities as it seeks to get CE mark, Australian and US approvals for its flagship product, the Evoke spinal cord stimulation (SCS) system.
Evoke has emerged from Saluda's platform technology, a closed-loop neuromodulation system that incorporates a bio-amplifier which continuously records the response of neurons to stimulation (called electrically evoked compound action potentials or ECAPS). The system uses this response to adjust the therapeutic dose of electrical stimulation and automatically deliver this optimum dose to the patient. Current SCS devices, unlike Evoke, do not have this feedback loop and can only give a fixed dose of stimulation. Any changes to the therapeutic regime have to be manually adjusted.
The 24-month Avalon study is currently assessing Evoke in patients with chronic pain of the trunk and/or limbs at five clinical sites in Australia. Preliminary three- and six-month findings from Avalon were presented by lead investigator Marc Russo, of Hunter Pain Clinic in New South Wales, Australia, at the International Neuromodulation Society meeting on May 29.
Of the 36 patients that were permanently implanted with Evoke, 31 patients were available for the three-month follow-up and their average improvement in overall pain was 79.3%. Of the 32 patients available at the six-month follow-up, the average improvement in overall pain 73.8%.
The proportion of subjects with ≥50% pain relief was 92.6% (3 months) and 85.0% (6 months) for back pain and 91.3% (3 months) and 78.6% (6 months) for leg pain. The proportion of subjects with ≥80% pain relief was 70.4% (3 months) and 65.0% (6 months) for back pain. and 56.5% (3 months) and 50.0% (6 months) for leg pain. .
Evoke was also associated with improvements in mean pain BPI scores, in quality of life, function and disability and sleep were observed. (See Figures 2 and 3). Additionally, interim programming visits decreased significantly over time, and the level of pain relief experienced by the patients treated with Evoke, at 3 months, in the Avalon study compared favorably to the pain relief at 3 months seen with other SCS systems in other clinical studies (See Figure 4).
The lead investigator told delegates at the INS congress that while the preliminary findings of a closed-loop SCS system using ECAPs were promising, there was still "a lot of potential for refinement to come." This included better prediction of outcomes and knowing the likelihood of a stimulation dose being effective for a particular patient, as well as being able to identify a neurophysiological signal for failure so the treatment can be preventative rather than reactive. (See Figure 5)
Evoke US Study: A Tonic To Standard SCS?
Saluda's series D financing will also go towards its US pivotal study, named after the SCS device itself. EVOKE is a randomized double-blinded trial which will compare Saluda's device against standard tonic SCS with fixed dose and no feedback loop. Discussing the details of the three-year study with INS congress delegates, lead investors of the Evoke trial and president of the INS, Timothy Deer of The Center for Pain Relief in West Virginia noted that tolerance and loss of therapy remains one of the last great hurdles in SCS and account for around 25% of explants of SCS devices. Conventional fixed-input SCS technologies do not adjust for the changing physiological conditions and real-time movement and the "encouraging data" from the Avalon study, which shows the potential of closed-loop SCS systems, is "a great step" in advancing neuromodulation as field, he told delegates.
Deer said that the Evoke study is notable in that it has been designed specifically to minimize the inherent bias in company-sponsored studies. The study used the same device for the control and the closed-loop arm and the clinicians, co-ordinators and research staff are blinded to the therapy. The patients are blinded to the hypothesis so they do not know the benefits of either arm of therapy, and their devices are programmed using the same technique and optimized using ECAPs. In the closed-loop arm, one extra step is taken to turn feedback on every five minutes or less.
Additionally, an independent adjudication committee will review all adverse events and an independent medical monitor will review all patients prior to enrollment.
Evoke will enroll around 134 patients in up to 20 sites across the US.