The panel voted 14 to 0 against granting de novo clearance to the device.
The US FDA Neurological Devices Panel of the Medical Devices Advisory Committee voted 14 to 0 against granting de novo clearance to Neuronix’s neuroAD Therapy System, a device intended to provide concurrent neurostimulation and cognitive training for the treatment of mild to moderate Alzheimer disease in patients who have a baseline Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score of no more than 30.
The device is approved for use in Europe, Australia, and Israel, but while the US FDA found that the device met safety standards, clinical trials didn’t prove its effectiveness. The company did not present post-market data from patients treated in countries where neuroAD Therapy System is approved.
“In the case of the neuroAD device, while it is a low risk device, it is difficult to
conclude that the available data demonstrates effectiveness or a clinical benefit. As a result, it is difficult to conclude that the benefits of the device outweigh the risks,” noted in the executive summary of the FDA panel.1 “Specifically, the FDA has significant concerns with the clinical data presented because the prespecified analysis of the pivotal study results favored the sham group over the treatment group and the post hoc analyses assessing device effectiveness carry significant uncertainty. There is uncertainty in the results of the post-hoc analysis of the pivotal study because the post-hoc analysis was conducted after the results of the trial were known, introducing bias. In the supplemental analyses there is uncertainty with respect to the conditions of study conduct (e.g., data collection, reporting and documenting of adverse events (some missing)) and the analysis methods (e.g., data pooling methodology, lack of pre-specified metrics to limit bias). In addition, the supplemental data and analyses presented show inconsistent results raising concerns that the observations are due to chance, rather than a true effect of the device treatment.”
Neuronix based its application on the results of a U.S. study where 130 participants with Alzheimer underwent either 6 weeks of daily treatment with neuroAD Therapy System and simultaneous cognitive training, or sham treatment without cognitive training. The subjects’ cognition was tested at 7 weeks and again at 12 weeks, with no treatment occurring after 6 weeks.
The non-invasive dual-stimulation device combines focused transcranial magnetic stimulation (TMS) with individualized cognitive training to stimulate target areas of the brain responsible for cognitive functions; the stimulation is designed to induce long-term potentiation. The device is designed to improve cognitive performance of patients, following an intervention period that lasts for 6 weeks, 5 days per week, with 1 hour-long sessions per day.
“We are pleased that the committee recognized the safety of the device, but we are disappointed that the panel’s feedback on our clinical studies and data analysis may result in neuroAD not being available in the US in the foreseeable future,” Eyal Baror, chief executive officer and president, Neuronix, said in a statement.2 “We plan to engage with the FDA to discuss a path forward to ensure that US patients have the same access to this treatment as is enjoyed by Alzheimer sufferers in over 30 other countries. On day when yet another Alzheimer drug trial was curtailed, we believe that this device offers a safe and effective nonpharmacologic solution to patients in need and are appreciative that the committee saw our data as a positive signal toward next steps.”
Risks associated with the neuroAD device appear to low and there were no device-related serious adverse events, however, a higher number of events occurred in the treatment group than sham group. In the pivotal study, mild device-related adverse events were experienced by 14% (11/79, includes the 20 non-randomized active patients) in the active group and 4% (2/50) in the sham group and included headache, neck pain, skin discomfort, and muscle twitching. In supplemental studies, potential risks included psychiatric symptoms, mild hearing impairment, blurry vision, eye pain, neck pain, mild scalp pain, achiness, fatigue, nausea, mild to moderate headaches, and anxiety.
In 2016, the system was granted an Expedited Access Pathway designation.
1. FDA Executive Summary. Prepared for the March 21, 2019 Meeting of the Neurological Devices Panel. De Novo DEN160053, Neuronix, Ltd., neuroAD™ Therapy System. fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/NeurologicalDevicesPanel/UCM633726.pdf.
2. neuroAD Therapy System for Treatment of Mild-to-Moderate Alzheimer's Disease Considered by FDA Neurological Devices Advisory Committee [news release]. Washington and Yoqneam, Israel: Neuronix Ltd.; March 22, 2019. prnewswire.com/news-releases/neuroad-therapy-system-for-treatment-of-mild-to-moderate-alzheimers-disease-considered-by-fda-neurological-devices-advisory-committee-300816952.html. Accessed March 25, 2019.