Nevro Corp. announced the publication of 24-month data from the SENZA Painful Diabetic Neuropathy (PDN) Randomized Controlled Trial (RCT), the largest RCT to evaluate spinal cord stimulation (SCS) to treat PDN, in Diabetes Research and Clinical Practice. Globally, the number of people with diabetes has quadrupled in the last two decades, and PDN is one of its most common complications, affecting up to 25% of all people with diabetes. PDN symptoms can have a significant impact on quality of life.

These symptoms include numbness, tingling/paresthesia, loss of protective sensation, impaired balance, and reduced response to sensory stimuli. Patients typically manage this complication with oral pain medications, but the efficacy of these medications is relatively low and can result in intolerable side effects for patients. As a result, people with PDN suffer significantly-reduced health-related quality of life (HRQoL), impaired functionality, and other comorbidities like sleep disorders, depression, and anxiety.

Published 24-month data from the SENZA-PDN RCT evaluated the long-term efficacy of high-frequency 10 kHz SCS to treat refractory PDN. The data show that patients who received a high-frequency 10 kHz SCS implant and conventional medical management (CMM), compared to CMM alone, experienced durable pain relief and significant improvements in both HRQoL and sleep at 24 months post-implantation. Furthermore, most participants experienced neurological symptom improvements, including those in motor, sensory, and reflex function.

The long-term data further supports that 10 kHz SCS is a safe and highly effective therapy for PDN, as well as a therapy that demonstrates durable quality of life improvements. The SENZA-PDN RCT 24-month data demonstrated the following benefits of 10 kHz SCS Therapy: Durable Pain Relief: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing =50% pain relief. A DN4 score =4 is consistent with clinically confirmed PDN.

In the 10 kHz SCS recipients, the proportion with a DN4 score <4 increased significantly from 3.9% at preimplantation to 48.9% at 24 months. (P < .001). Neurological Improvements: Investigators assessed neurological function versus study baseline in all implanted patients.

At 24 months, 65.7% of implanted patients exhibited clinically meaningful improvements over study baseline in sensory, motor, or reflex function without worsening in any category. A majority of these neurological improvements were in sensory function, which may have implications in restoring protective sensation. No other SCS treatment for PDN has exhibited the potentially disease-modifying effects demonstrated by Nevro HFX?

in improving neurological function. HRQoL: HRQoL significantly improved with 10 kHz SCS, based on the EuroQol 5-Dimensional 5-Level (EQ-5D-5L) questionnaire. Among all implanted patients, the mean EQ-5D-5L index value increased by 0.146 from preimplantation to 24 months, which is 2.9 to 4.9 times the minimally important difference for people with type 2 diabetes.

Pain Interference with Sleep: Baseline sleep quality was poor among all study participants, as shown by a mean score on the Pain and Sleep Questionnaire 3-Item Index (PSQ-3; 0-10 cm scale) of 6.5 cm at preimplantation. Treatment with 10 kHz SCS significantly reduced pain interference with sleep in the group of all implanted patients over 24 months, as demonstrated by a 65.5% decrease in the mean PSQ-3 score, from 6.5 at preimplantation to 1.9 at 24 months. Safety: The incidence and type of procedure-related complications were comparable to those reported in the SCS literature for all patient populations.

Five (3.2%) SCS systems were explanted due to infection, and no devices were explanted due to lack of efficacy. Consistent Outcomes: Comparable to the 6- and 12-month SENZA-PDN study outcomes, the 24-month results confirm robust and long-lasting beneficial effects of 10 kHz SCS in PDN patients. These are important findings, given the severe, chronic, and debilitating nature of PDN and the lack of effective treatment options for this patient population.

Nevro's SENZA-PDN trial is the largest RCT conducted to date studying SCS therapy for PDN patients, enrolling 216 patients with refractory PDN. In total, 142 patients implanted with Nevro's high-frequency (10 kHz) SCS system, Nevro HFX, were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. This study aimed to provide high-level evidence to aid clinical decision-making, albeit with some limitations, including risks of biased outcomes and potential placebo effects, the potential impact of missed follow-up visits on study results, and limitations related to interpreting the observed neurological improvements.