The approval adds medication-refractory tremor from Parkinson disease to the current indication for incisionless, focused ultrasound thalamotomy.
Jeff Elias, MD
The Center for Devices and Radiological Health of the FDA has approved an expansion of Insightec’s indication of Exablate Neuro to include treatment of patients with tremor-dominant Parkinson disease.
The system utilizes focused ultrasound to target and ablate tissue in the brain with no surgical incisions as MRI guides treatment planning, delivering thermal feedback for real-time monitoring allowing for a personalized treatment plan. Patients of the therapy must be at least 30 years of age. The approval adds medication-refractory tremor from Parkinson disease to the current indication for incisionless, focused ultrasound thalamotomy.
“This is another validation of a great technology,” Jeff Elias, MD, University of Virginia School of Medicine, said in a statement.1 “Patients are attracted to the less invasive aspects of focused ultrasound. Now Parkinson patients, for whom tremor is their primary disability, have more treatment options than conventional cranial surgery. While focused ultrasound is not curative for Parkinson disease, it can provide significant quality of life benefits. Research continues for the other symptoms of Parkinson.”
The approval is based on data from a randomized clinical trial that examined the safety and efficacy of focused ultrasound thalamotomy for managing medically refractory, tremor-dominant Parkinson and measured the magnitude of the placebo response.2 The pilot trial studied 27 participants with tremor-dominant Parkinson disease and randomized them 2:1 to focused ultrasound thalamotomy (20 participants) or a sham procedure (7 participants). Twenty-six participants were male (96%), and the median age was 67.8 years. Participants were clinically assessed at baseline and 1, 3, and 12 months post treatment; posttreatment MRI was performed postprocedure day 1, 30, and 1 year.
The predefined primary efficacy outcome was the difference in improvement between the arms at 3 months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor, while the primary safety outcome was assessed by monitoring the incidence and severity of the procedure-related adverse effects from the procedure through 1 year after treatment. Cognition and mood were monitored with the Beck Depression Inventory and Montreal Cognitive Assessment at baseline, 3 months, and 12 months. Secondary outcomes included descriptive results of the Unified Parkinson’s Disease Rating Scale scores and quality of life measures.
The results of the study revealed that on-medication Clinical Rating Scale for Tremor A+B treated hand tremor subscores improved a median 7 points or 62% (interquartile range (IQR), 22%—79%) from a baseline of 17 points (IQR, 10.5–27.5) following focused ultrasound thalamotomy and 2 points or 22% (IQR, -11% to 29%) from a baseline of 23 points (IQR, 14–27) after sham procedures, a statistically significant difference. The on-medication median Unified Parkinson’s Disease Rating Scale motor scores improved 8 points (IQR, 0.5–11.0) from a baseline of 23 points (IQR, 15.5–34.0) following FUS thalamotomy and 1 point (IQR, −5.0 to 9.0) from a baseline of 25 points (IQR, 15.0–33) after sham procedures.
Overall, focused ultrasound thalamotomy for patients with tremor-dominant Parkinson disease demonstrated improvements in medication-refractory tremor by Clinical Rating Scale for Tremor assessments, even in a placebo setting response.
The most common adverse effects of the focused ultrasound thalamotomy procedure were finger paresthesia, ataxia and orofacial paresthesia, and most often, these were mild or transient but persistent paresthesia and ataxia occurred in 19% and 4%, respectively.
One of the limitations of the study was that the trial was limited by a small size and the planned study enrollment of 30 participants was not reached. Additionally, while the pilot trial suggests preliminary efficacy for the management of medication-refractory, tremor-dominant Parkinson disease, a substantial placebo response was reported.
Exablate Neuro, approved by the FDA in July 2016, is the first focused ultrasound device to receive approval for treatment of medication-refractory essential tremor with non-invasive MR-guided focused ultrasound thalamotomy.
1.INSIGHTEC Announces FDA Approval of Exablate Neuro for the Treatment of Tremor-Dominant Parkinson's Disease [news release]. Haifa, Israel, and Miami, Fla.: Insightec; Dec. 18, 2018. https://www.prnewswire.com/news-releases/insightec-announces-fda-approval-of-exablate-neuro-for-the-treatment-of-tremor-dominant-parkinson-s-disease-874689536.html?rel=0" ?rel=0" . Accessed Dec. 18, 2018.
2. Bond A, Shah B, Huss, D, et al. Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease. JAMA Neurology. 2017;74(12):1412­—1418.