FDA Approves Neuroimmune Modulation Therapy for Rheumatoid Arthritis

The FDA has approved SetPoint Medical’s SetPoint System novel neuroimmune modulation therapy device for the treatment of adults living with moderate-to-severe rheumatoid arthritis (RA) who are not adequately managed by or cannot tolerate existing advanced RA therapies, such as biological and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs).1

“The approval of the SetPoint System highlights the potential of neuroimmune modulation as a novel approach for autoimmune disease, by harnessing the body’s neural pathways to combat inflammation,” principal investigator Mark Richardson, MD, PhD, Director of Functional Neurosurgery at Massachusetts General Hospital and Professor of Neurosciences at Harvard Medical School, said in a statement.1 “After implantation during a minimally invasive outpatient procedure, the SetPoint device is programmed to automatically administer therapy on a predetermined schedule for up to 10 years, simplifying care for people living with RA.”

The SetPoint System is an implantable, integrated neurostimulation device that delivers electrical stimulation to the vagus nerve once daily, to activate the body’s innate anti-inflammatory and immune-restorative pathways. The therapy offers a treatment option without immune-compromising risks to patients with RA.

The FDA’s approval was supported by data from 242 participants in the randomized, double-blind, sham-controlled, RESET-RA study, that demonstrated the device’s safety and efficacy.

“This is a landmark study in the treatment and care of rheumatoid arthritis,” said John Tesser, MD, FACP, FACR, MACR, a leading rheumatologist and national rheumatology principal investigator of the RESET-RA study.1 “The study met its primary efficacy endpoint of ACR20 at three months, with improvements observed in ACR response rates and disease activity metrics through 12 months of follow-up. 75% of patients in the study were free of biologic or targeted synthetic DMARDs at 12 months.”

Over 60% of RESET-RA’s participants had difficult-to-treat RA. Investigators found that ACR20 response at Week 12 showed a statistically significant difference favoring the treatment group (35.2%) compared with the sham control group (24.2%; P = .0209; 95% CI, 0.6-23.1). After week 12, all patients were crossed over to receive SetPoint therapy and at 24 weeks, ACR20 responses in patients on SetPoint therapy without added b/tsDMARD, was 51.5% in the treatment group and 53.1% in the crossover group.2

A pre-specified subgroup analysis found that among patients with 1 prior b/tsDMARD exposure (39% of participants), ACR20 response at Week 12 was 44.2% with treatment versus 19.0% with control (P = .0054; 95% CI, 7.1–43.3). Patients receiving SetPoint therapy were also more likely to achieve low disease activity or remission (DAS28-CRP <3.2) at 12 weeks compared with control (P = .0154). RAMRIS analysis showed that in the 1 prior b/tsDMARD subgroup, bone erosion progressors (>0.5 change in erosion score) were reduced by 74% with treatment (P = .0099), and in the highly erosive phenotype subgroup, progressors were reduced by 50% (P = .016). By week 24, 81% of patients remained on SetPoint therapy without adding steroids or additional b/tsDMARDs.2

The SetPoint System had a manageable safety profile with a low rate (1.7%) of serious adverse events (SAE) through the first 12 weeks which decreased to 0% to 24 weeks. The most common related AR was mild to moderate hoarseness (vocal cord dysfunction) associated with the implantation procedure. No participants discontinued due to adverse events.2

“The approval of the SetPoint System, the first-in-class neuroimmune modulation platform, represents a transformative milestone in the management of autoimmune diseases,” Murthy V. Simhambhatla, PhD, CEO of SetPoint Medical, said in a statement.1 “We are committed to improving the health of people living with RA, and look forward to working with providers and payers to make our innovative therapy accessible to their patients. We plan to introduce the SetPoint System in targeted US cities this year, followed by expansion across the country starting in early 2026.”

REFERENCES

1. SetPoint Medical Receives FDA Approval for Novel Neuroimmune Modulation Therapy for Rheumatoid Arthritis. News release. SetPoint Medical. July 31, 2025. https://setpointmedical.com/setpoint-medical-receives-fda-approval-for-novel-neuroimmune-modulation-therapy-for-rheumatoid-arthritis/

2. SetPoint Medical Announces Late-Breaking Data from RESET-RA Study at ACR Convergence 2024. News release. Novemeber 18, 2024. https://setpointmedical.com/setpoint-medical-announces-late-breaking-data-from-reset-ra-study-at-acr-convergence-2024/