Carthera has enrolled the first 100 patients in its SONOBIRD pivotal trial, marking a significant milestone in what will be the largest clinical trial ever conducted using ultrasound technology to temporarily open the blood-brain barrier (BBB) in patients with recurrent glioblastoma.
The Paris-based medical device company, a spin-off from Sorbonne University founded by neurosurgeon Prof. Alexandre Carpentier, is evaluating its innovative SonoCloud® device in combination with carboplatin chemotherapy against standard-of-care treatments for patients experiencing their first glioblastoma recurrence.
Nearly all 40 participating clinical sites across Europe and the United States are now actively recruiting, with the company projecting swift enrollment to reach the planned 560-patient target. The trial began in February 2024 and aims to complete enrollment within two years.
Revolutionary Approach to Brain Cancer Treatment
Glioblastoma remains one of the most aggressive and treatment-resistant brain cancers, with limited therapeutic options upon recurrence. The blood-brain barrier, while essential for protecting the brain from harmful substances, also prevents most chemotherapeutic agents from reaching tumors at effective concentrations.
The SonoCloud system addresses this fundamental challenge through an implantable device that emits low-intensity ultrasound waves. When activated before chemotherapy administration, it temporarily increases the permeability of blood vessels in the brain for approximately six hours, potentially allowing higher concentrations of therapeutic agents to reach the tumor.
"We desperately need new treatments for patients with recurrent glioblastoma. SonoCloud has the potential to transform our ability to deliver a high dose of therapeutics to the brain," said Dr. Marjolein Geurts, neuro‐oncologist at Erasmus Medical Center Cancer Institute in Rotterdam, Netherlands.
Trial Design and Clinical Significance
The SONOBIRD trial (NCT05902169) represents the world's first randomized, multicentric, two-arm pivotal study of BBB opening prior to chemotherapy in recurrent glioblastoma patients. The open-label study randomizes patients in a 1:1 ratio to receive either:
- SonoCloud-facilitated BBB opening with carboplatin chemotherapy
- Standard therapies (lomustine or temozolomide)
The primary endpoint is overall survival, with secondary measures evaluating the effectiveness of the SonoCloud and carboplatin combination in delaying or slowing tumor growth.
Dr. Brian Gill, assistant professor of neurosurgery at Columbia University Irving Medical Center in New York, noted: "It has been a privilege to offer this trial to patients with recurrent glioblastoma. The underlying concept is highly promising, device implantation has proceeded smoothly and patients have shown strong interest in participating."
Clinical Experience and Regulatory Status
To date, more than 550 SonoCloud treatments have been performed worldwide, establishing Carthera as a leader in ultrasound-based BBB opening technology. The SONOBIRD trial builds upon the earlier SC9-GBM-01 study, which demonstrated the feasibility and safety of SonoCloud, as well as the potential of carboplatin when combined with BBB opening.
The SonoCloud system received FDA Breakthrough Device Designation in 2022 and both FDA and EMA Orphan Drug Designation in 2023 for carboplatin when used with the device. These designations acknowledge the technology's potential to address an unmet medical need in a serious condition.
"Achieving this milestone is an important step in introducing our SonoCloud device to the large patient population urgently in need of solutions to improve treatment outcomes," said Frederic Sottilini, CEO of Carthera. "With its breakthrough device and orphan drug designations, Carthera remains committed to transforming glioblastoma treatment and to obtaining market access for its groundbreaking technology."
How SonoCloud Works
The SonoCloud device is surgically implanted into the skull and activated prior to chemotherapy administration. Several minutes of low-intensity ultrasound temporarily disrupts the tight junctions between endothelial cells in the brain's blood vessels, creating a window of opportunity for therapeutic molecules to cross into brain tissue.
This ultrasound-induced opening of the blood-brain barrier represents a world-first approach and could potentially offer new treatment options for various neurological conditions beyond glioblastoma, including Alzheimer's disease.
Carole Desseaux, Chief Clinical Officer at Carthera, emphasized the collaborative nature of the trial: "Our progress in recruiting patients reflects the engagement and strong support from our clinical sites, and from the neuro-oncology and surgery community, in advancing innovative therapies. We are very grateful for the commitment and enthusiasm of the patients and clinicians who are taking part in this trial."
The first interim analysis of the clinical data is expected to be available soon, with the registrational study aiming to support future marketing authorization applications.
