Research

In recent news, data from a long-term, follow-up study (NCT01827904) assessing Insightec’s unilateral MR guided focused ultrasound (MRgFUS) surgery (thalamotomy) for essential tremor (ET) showed sustained and significant tremor improvement at 5 years.

Results from the study suggest the unilateral MRgFUS thalamotomy using their Exhalate System is an effective treatment for patients with intractable ET, with significant long-term durability to back data. With the data, the company also announced the FDA approval of the 5-year study end point for the study, considered the largest prospective long-term trial of MRgFUS to date. Among 85 treated-patients outcomes per the Clinical Rating Scale for Tremor (CRST) scores for postural tremor remained significantly improved by 73.3% and 73.1% from baseline at 48 and 60 months posttreatment, respectively (both, P <0.0001). Similarly, combined hand tremor/motor scores also showed significant improvement by 49.5% and 40.4% (P <0.0001) at each of the respective time points.

The FDA approval validates the years of work that we have invested into using Focused Ultrasound as a front-line therapy for ET,” Maurice R. Ferre, MD, chief executive officer and chairman of the Board of Directors, Insightec, said in a statement.

It also substantiates that using MR- guided focused ultrasound to treat essential tremor is safe and effective, as well as long-lasting. We look forward to making further progress in finding more uses for focused ultrasound and building on the success of the treatment of essential tremor.

The randomized, controlled, multi-center study investigated the long-term safety and efficacy of unilateral MRgFUS thalamotomy at 4- and 5-years posttreatment for medication-refractory essential tremor using the Exablate System. In the study, 45 and 40 patients completed the 4- and 5-year follow-ups, respectively. The CRST scores, including postural tremor scores (Part A), combined hand tremor/motor scores (Parts A and B), and functional disability scores (Part C), were measured by a neurologist and the Quality of Life in Essential Tremor Questionnaire (QUEST) assessed quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared with baseline to assess treatment efficacy and durability. Notably, functional disability scores increased slightly over time, although remained significantly improved for 5 years (P <0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (P <0.0001) and year 5 (P <0.0003).

All of the previously reported adverse events (AEs) remained mild or moderate, with no new AEs related to the procedure reported from the 12 month timepoint to the last follow-up at 5 years. This study also confirms the long- term efficacy of the procedure for patients with ET, following its FDA approval for the treatment of the second side tremor in patients with essential tremor. The device was originally approved for the treatment of medication- refractory ET in 2016 and with this more recent approval, it allows appropriate patients to have their second side treated at least 9 months after treatment of the first side. The basis for the new indication came from a 51 patient cohort study that spanned 7 academic medical centres in the US over a 6 month period.

There, investigators observed significant reductions in tremor in the second side of patients immediately following treatment with Exablate, which was sustained through at least 6 months of follow up. Notably, these findings were consistent with the first side treated. In the study, there was a significant improvement in functional disability and the safety profile was similar to the first side, with the majority of adverse events being mild in nature. Using a helmet-shaped ultrasound inducer, the Exablate Neuro device also has adjustable advanced focusing algorithms to ensure beams converge at the desired target on the patient’s skull. The process is performed on an outpatient basis in an MRI suite, with treatment guided by MR imaging. The initial FDA approval, granted in 2016, made Exablate Neuro the first FUS device to receive approval for the treatment of medical-refractory ET with non-invasive MR guided FUS thalamotomy.