Author: Rachael Hansford

Carthera receives FDA breakthrough device designation for SonoCloud-9 system, allowing for enhanced interaction with FDA and recognising SonoCloud system as innovative and promising approach for treatment of recurrent glioblastoma

Carthera, a French company that designs and develops SonoCloud, an ultrasound-based medical device to treat a wide range of brain diseases, announced on June 22 2022 that its SonoCloud-9^® system has been listed as a Breakthrough Device by the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration (FDA).

 The SonoCloud device uses low intensity pulsed ultrasound to temporarily disrupt the Blood-Brain Barrier (BBB), to allow higher brain exposure to therapeutic compounds. By using SonoCloud, the therapeutic efficacy of new and existing therapies can be unlocked and harnessed to improve the treatment of a wide range of brain diseases, such as glioblastoma.
 
“There is a significant unmet need for new treatments for glioblastoma patients, who have very few available therapeutic options,” said Michael Canney, chief scientific officer at Carthera. “We’re excited that the FDA has acknowledged the innovative potential of the SonoCloud approach through the granting of this Breakthrough Designation.”
 
The Breakthrough Devices Designation, intended to expedite the development and review of the medical device, was based on preliminary phase 1/2a clinical data that indicates substantial improvement over available second-line therapy (publication under preparation).
 
“The FDA Breakthrough Device Designation will help Carthera to efficiently advance to a pivotal trial and Premarket Approval (PMA),” said Sandra Thiollière, head of quality and regulatory affairs at Carthera. “We look forward to working closely with the FDA through this accelerated process to bring SonoCloud to patients with recurrent glioblastoma.”
 
This designation will give Carthera access to priority review, more intensive FDA interaction to build an efficient device development programme and commitment from experts and senior managers from the FDA, who will assist the company in addressing any potential challenges during the premarket review phase.

“Following the recent successful completion of our phase 1/2 trial in recurrent glioblastoma, this Breakthrough Device Designation is another important milestone supporting the potential of SonoCloud.”

Frédéric Sottilini, CEO of Carthera.

About SonoCloud-9
The SonoCloud-9 device is implanted in a skull window, below the skin; once in place it is invisible. When activated for few minutes using a transdermal needle connection to an external control unit, the BBB is disrupted for several hours; a window during which drug therapies can be administered. By administering therapies when the BBB is disrupted, drugs can reach the brain in higher and more effective concentrations. This treatment can be repeated at each cycle of drug therapy.
 
About the FDA Breakthrough Device Programme
The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to certain medical devices by speeding up their development, assessment and review, while preserving the statutory standards for Premarket Approval, 510(k) clearance and De Novo marketing authorization, consistent with the Agency’s mission to protect and promote public health.

A new study has shown that plasticity-based brain training can drive improvements in patients with persistent symptoms of Traumatic Brain Injury (TBI). Gains were observed in standard measures of cognition, standard measures of self-reported symptoms, and the connectivity between brain regions. The intervention used in the study was brain exercises from BrainHQ, made by Posit Science.

Traumatic Brain Injury affects millions of Americans every year, with an estimated 2.5 million treated in emergency rooms. Most recover fully, but for some, the symptoms persist for years and disrupt earning a livelihood and personal relations. An estimated two percent of Americans live with these long-term effects.

Researchers at New York University enrolled 21 patients with chronic TBI that had persisted, on average, for more than seven years. Patients were diagnosed with mild, moderate, or severe TBI, and assigned to either an intervention group or a control group. The intervention group was asked to complete a total of 40 hours of training over 13 weeks (or about 3 hours per week). Before and after the 13-week period, cognitive function was measured with standardised neurocognitive tests, and brain connectivity was measured with fMRI brain imaging.

The researchers found that the brain training group showed significant improvements in standard cognitive tests of attention, memory, and executive function, as well as in standard measures of self-reported symptoms, as compared to the control group. Imaging revealed significant improvement in the functional connectivity across a key network of brain regions – known as the Default Mode Network (DMN). Lower connectivity is associated with cognitive dysfunction and deficits.

“This new study confirms and extends what has been seen in seven prior studies of chronic TBI and BrainHQ, which have shown study participants improved measures of cognitive abilities and symptoms, with imaging showing functional re-organization of the brain” observed Dr. Henry Mahncke, CEO of Posit Science.

These type of persistent symptoms — following not just Traumatic Brain Injuries, but other types of injuries such as “chemobrain,” “cardiobrain,” and “long COVID” — are increasingly known as “brain fog.” Researchers increasingly believe that common brain mechanisms underly the brain fog seen across these disparate conditions – which may explain the similar pattern of results seen in three studies of BrainHQ in cancer patients and seven studies in heart failure patients showing similar types of improvement.

More than 100 published studies of the exercises in BrainHQ have shown benefits, including gains in standard measures of cognition (attention, speed, memory, executive function, social cognition), in standard measures of quality of life (mood, confidence and control, managing stress, health-related quality of life) and in real world activities (gait, balance, driving, everyday cognition, maintaining independence). BrainHQ is now offered, without charge, as a benefit by leading national and 5-star Medicare Advantage plans and by hundreds of clinics, libraries, and communities. Consumers can also try BrainHQ for free at http://www.brainhq.com.

The U.S. Food and Drug Administration (FDA) has granted De Novo marketing authorisation for Fujirebio Diagnostics’ Lumipulse^® G β-Amyloid Ratio (1-42/1-40) in vitro diagnostic (IVD) test for the assessment of β-Amyloid pathology in patients being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline. The test, which was granted Breakthrough Device Designation by the FDA, is the first FDA-authorised in vitro diagnostic test in the U.S. to aid in the assessment of Alzheimer’s disease and other causes of cognitive decline.

Alzheimer’s disease is a leading cause of disability and death internationally, but current diagnostic methods are limited. AD develops over many years, long before symptoms are evident, but the lack of accessible diagnostics results in many patients remaining undiagnosed until the disease is well advanced, when few effective interventions remain.

A key feature of AD is the presence of β-Amyloid plaques in the brain. β-Amyloid plaques are believed to contribute to the loss of cognitive function that characterises AD, but accurately evaluating amyloid pathology has been difficult. Clinicians have relied primarily on cognitive assessments, including standardised cognitive screening tests. However, in early stages of the disease, a diagnosis of Alzheimer’s disease relying primarily on cognitive tests has been shown to be incorrect in approximately 50-60% of patients¹. The Lumipulse G β-Amyloid Ratio (1-42/1-40) offers an alternative to the current standard for determining amyloid-pathology, amyloid positron emission tomography (PET) brain imaging which is expensive, subjective, time consuming, inaccessible to many Americans, and often not covered by health insurance.

The Lumipulse G β-Amyloid Ratio (1-42/1-40) test is an accurate, minimally invasive, accessible measure of β-Amyloid that can detect the formation of amyloid plaques early in the disease. It is intended for use in adult patients aged 55 years and older presenting with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The β-Amyloid Ratio test measures the concentrations of β-Amyloid 1-42 and β-Amyloid 1-40 in the CSF to calculate a numerical ratio as a proxy for the presence of β-Amyloid plaque in the brain.

“FDA authorisation of the Lumipulse G β-Amyloid Ratio (1-42/1-40) test and the upcoming U.S. launch are important milestones in the campaign to transform AD into a manageable disease,” says Monte Wiltse, President and CEO at Fujirebio Diagnostics, Inc. “Patients, physicians and families now have a valuable new tool to help identify those individuals whose early symptoms may be indicative of AD, providing the opportunity to adopt life style changes and potentially to access new therapies aimed at slowing or stopping disease progression. FDA authorisation of this first IVD biomarker test reflects our ongoing commitment to working with the healthcare community and AD advocates to achieve significant progress against this devastating disease.”

William Hu, MD, PhD is Chief, Division of Cognitive Neurology at Robert Wood Johnson Medical School and Principal Investigator of the Hu Lab, which focuses on researching fluid biomarkers for AD and other neurodegenerative disorders. Dr. Hu says, “The development of accurate tests for AD using biomarkers found in the CSF or other bodily fluids is a requirement if we are to make real progress against this dreaded disease. The importance of early diagnosis in AD is widely acknowledged, but until now, there has been no approved biomarker test available to clinicians and patients. FDA authorisation of the Fujirebio β-Amyloid Ratio test is a significant advance that marks the advent of a new era, facilitating more efficient clinical trials for new AD therapies and enabling patients and their doctors to make more informed decisions and take action much earlier in the disease process.”

The Lumipulse G β-Amyloid Ratio (1-42/1-40) test is not intended as a screening or standalone assay to diagnose AD. Results must be interpreted in conjunction with other patient clinical information. The assay is analysed on Fujirebio’s fully automated Lumipulse G1200 instrument system.

www.fujirebio.com.

References

1. Schneider, Julie A. Arvanitakis, Z. Leurgans, S.E. Bennet DA. The Neuropathology of Probable Alzheimer’s Disease and Mild Cognitive Impairment. Ann Neurol. 2009;66(2):200-208. doi:10.1002/ana.21706.

2. Gobom J, Parnetti L, Rosa-Neto P, et al. Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid. Clin Chem Lab Med. 2022;60(2):207-219. doi:10.1515/cclm-2021-0651.