The positive data for SetPoint Medical’s neuromodulator in Crohn’s disease are, like those it posted in rheumatoid arthritis, early but encouraging. The implant stimulates the vagus nerve to reduce inflammation, and if this seems unusual it is: a search of EvaluateMedTech reveals it to be the only medical device-based approach to the treatment of Crohn’s (see table below).
But SetPoint’s tiny open-label pilot study is hardly conclusive, and approval of the stimulator cannot come before 2019 anyway, even though the device would require much smaller clinical trials than are needed for drugs. The Glaxo-backed start-up still has a way to go.
The device delivers electrical impulses to the vagus nerve in the neck, which SetPoint says can block the production of inflammatory cytokines including TNF; essentially it works in the same way as the blockbuster anti-inflammatory antibodies (SetPoint off to a good start in the clinic, July 21, 2016).
SetPoint’s trial enrolled eight patients with severe Crohn’s disease who were not responsive to or intolerant of TNF inhibitors. After 16 weeks’ treatment, six of the eight patients had scores on the Crohn's Disease Activity Index reduced by 70 points or more. Three had endoscopic remission, their intestinal lining appearing healthy.
The company is touting this as a significant reduction in Crohn’s symptoms. Severe Crohn’s is defined by a CDAI score of more than 450, and remission as below 150; in drug trials clinical response is defined as reduction in CDAI score by at least 100 points.
The data also show a direct correlation between vagus nerve stimulation and the suppression of pro-inflammatory cytokines including TNF, the company said. SetPoint believes that its stimulator – actually manufactured by Cyberonics (now LivaNova), although an in-house version is under investigation – is a better bet than drug therapy, as TNF alpha inhibitors lose efficacy over time.
It will take a lot more clinical data to prove the technology better than antibodies. But, if it can pull this off, SetPoint will probably have the medtech angle to Crohn’s all to itself. All the other studies of medical technologies in the disease are of imaging technologies.
|Selected Crohn’s disease device trials|
|Company||Device||Conditions||Enrolment||Primary completion||Country||Trial ID|
|SetPoint Medical||Vagus Nerve Stimulation Device||Crohn’s disease||15||Aug 2016||Netherlands||NCT02311660|
|iThera Medical||Multispectral Optoacoustic Tomography||Crohn’s disease
|Smart Medical Systems||NaviAid AB||Inflammatory bowel diseases
|Medtronic||PillCam SBC system||Chronic inflammatory small bowel disease
|Medtronic||PillCam Colon 2 Capsule Endoscopy||Crohn’s disease||34||Feb 2017||Australia||NCT02624414|
SetPoint’s stimulator could gain CE mark in Europe for arthritis in 2018, with US approval a year or so later. Approval for Crohn’s is probably tracking a year behind that schedule.
A new cohort of patients is now being recruited into the Crohn’s study, but further trials will need to be bigger and feature some sort of blinded sham control, as well as focusing more on objective biomarkers such as cytokine levels rather than disease questionnaires.
That will require funding. Having major strategic investors is a good start – as well as Glaxo, Medtronic, Abbott and Boston Scientific have also pumped cash into SetPoint – and the company is working towards a $60m series D. The device will have to ace future trials to justify that level of investment.