SetPoint Medical has received FDA investigational device exemption (IDE) approval to conduct a pilot study of its neuroimmune modulation platform in patients with relapsing-remitting multiple sclerosis (RRMS). The multicenter, randomized, double-blind, sham-controlled trial is set to begin in 2025 and will enroll up to 60 participants across the United States. This innovative approach aims to address a critical unmet need in MS treatment: promoting nerve repair and neuroprotection, rather than solely suppressing immune activity.
Neuroimmune Modulation: A Novel Approach
Traditional disease-modifying therapies (DMTs) for relapsing MS primarily focus on reducing the frequency and severity of relapses by modulating the immune system. However, these therapies often fall short in addressing the progressive loss of myelin sheaths around nerve fibers, a hallmark of MS pathology. SetPoint's neuroimmune modulation platform offers a different approach by activating neural reflex arcs that allow the brain to communicate with the immune system to maintain immune homeostasis.
According to David Chernoff, MD, chief medical officer at SetPoint, the platform delivers targeted electrical stimulation to the vagus nerve, the longest of the 12 cranial nerves, to activate these innate pathways. This stimulation modulates immune responses without causing broad immunosuppression, a common side effect of many MS drugs that increases infection risk. Instead, it partially reduces the ability of white blood cells to secrete pro-inflammatory cytokines.
Potential for Remyelination and Neuroprotection
Beyond its anti-inflammatory effects, neuroimmune modulation also has the potential to promote neuroprotection and remyelination. Stimulation of the vagus nerve releases specialized pro-resolving mediators that aid in clearing cellular debris and upregulating genes involved in remyelination. This is particularly significant in MS, where demyelination contributes significantly to disease progression and disability.
Preclinical studies in rodent models have shown that neuroimmune modulation not only reduces disease activity but also demonstrates a strong signal for remyelination, an effect not typically observed with existing MS drugs. The upcoming clinical trial will focus on evaluating the remyelinating properties of SetPoint's device in RRMS patients.
Clinical Trial Design and Endpoints
The pilot study will enroll RRMS patients with stable disease who have deficits in their visual and other functional pathways despite being on DMTs. Participants will be implanted with the SetPoint system and randomized to either active stimulation or sham stimulation for six months. After this period, all participants will have the option to receive active stimulation and be followed up long-term.
The trial will assess a range of endpoints to evaluate the potential of remyelination, including safety assessments and serial assessments of visual pathways using optical coherence tomography (OCT), visual evoked potentials (VEP), and visual acuity. Brain MRI quantification of myelin using magnetization transfer ratio (MTR) will also be performed.
Prior Evidence and Safety Profile
SetPoint's neuroimmune modulation platform has previously been evaluated in the RESET-RA study, which focused on patients with rheumatoid arthritis (RA). The study demonstrated that the implant procedure is safe, with low rates of procedure, device, or stimulation-related adverse events. It also showed the anti-inflammatory and joint-protective potential of neuroimmune modulation in RA patients. These findings support the safety and feasibility of further development of the platform for other autoimmune and inflammatory conditions, including MS.
