Synergia Medical advanced the NAO.VNS program across manufacturing, preclinical validation, regulatory approval, and clinical deployment. The main objective was to demonstrate safety and usability in a First-in-Human (FiH) study and prepare for a pivotal clinical trial.
Manufacturing and Technical Validation
A risk-based validation strategy was applied to production equipment and processes. Critical assembly, inspection, and manufacturing tools used by Synergia were qualified or calibrated according to ISO13485 requirements. The production process for both the implantable pulse generator and optical lead was qualified, with 100% quality inspection implemented where stability remained limited. Twelve sterile implant systems were successfully manufactured and released for clinical use. Following FiH and technical validation, an improvement in optical compatibility across components reduced the need for pair-matching, reducing the pivotal study production requirement from 300 to 100 systems. While manufacturing is postponed to 2026 in line with the updated roadmap, design and technical readiness of the product for clinical usage is demonstrated despite suboptimal production process performances..
Preclinical and Regulatory Progress
All preclinical safety assessments were completed, including biological safety testing, electromagnetic compatibility, usability validation, and software verification, with results meeting acceptance criteria. Two GLP-compliant in vivo studies confirmed good tolerance, functional stimulation, and device reliability in sheep models. On this basis, a complete design dossier was submitted to the Belgian authorities in February 2024, leading to regulatory and ethics approval of the FiH study in April 2024.
First-in-Human Clinical Achievements
The FiH AURORA study enrolled and implanted five adult patients with drug-resistant epilepsy at two Belgian sites. Although authorization was granted for up to ten patients, a protocol-defined interim analysis at six months confirmed the primary safety endpoint, and enrollment was closed. No serious adverse events, serious adverse device effects, or unanticipated device effects were reported. Side effects such as mild hoarseness, cough, or tingling were transient and consistent with known VNS therapy. Surgical teams reported smooth implantation and good usability of the device and accessories. Three implantation-related adverse events (light awakening during surgery, foreign body reaction to a suture, and a mild granuloma) resolved or were clinically benign. At six months, patients showed a 40% seizure responder rate, seizure severity improvements in 60% of cases, quality-of-life improvements in 80%, and mood improvements in all patients with baseline depressive symptoms.
Conclusion
The project achieved its core technical, regulatory, and clinical objectives. The NAO.VNS system was validated in preclinical and FiH studies, showing strong safety, good usability, and early clinical benefit. Manufacturing readiness is planned to support submission and initiation of next clinical phase in 2026 assuming appropriate level of financing is secured.
