Alpheus Medical Advances to Phase 2b Testing of Experimental Brain Cancer Therapy

Alpheus Medical has enrolled 10 patients in a Phase 2b, randomized controlled trial, marking early momentum in evaluating a novel, non-invasive, drug-centered therapeutic approach to one of the most difficult-to-treat brain cancers.

Glioblastoma is a highly infiltrative brain tumor in which cancer cells extend well beyond visible tumor margins, spreading throughout the affected brain hemisphere. This diffuse nature fundamentally limits the effectiveness of surgery and localized therapies, leaving newly diagnosed patients with few meaningful treatment options and historically poor long-term outcomes.
To address this challenge, Alpheus Medical is evaluating an investigational therapy based on Porphyrin Metabolite Activation (PoMA)¹ — an approach

previously described in clinical literature as Sonodynamic Therapy. The strategy is drug-centered, leveraging a molecule that preferentially accumulates in tumor cells, which is then activated using low-intensity, diffuse ultrasound to enable localized pharmacologic effects across the affected hemisphere.

"Glioblastoma patients have few effective treatment options and poor long-term outcomes, highlighting the urgent need for innovation," David Reardon, MD, director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and principal investigator of the study, said in a press release. "Alpheus' approach is designed to address the diffuse nature of the disease by enabling treatment across the affected hemisphere. We look forward to generating data to understand its potential role in patient care."

A Drug-Centered Strategy for a Diffuse Disease

Unlike localized interventions, PoMA is designed to activate the therapeutic molecule directly within tumor cells while minimizing systemic exposure. By using low-intensity ultrasound to trigger the drug throughout the hemisphere—rather than targeting a defined tumor boundary—the approach attempts to reach the infiltrative cancer cells that conventional surgery and radiation cannot.

Preclinical and early clinical rationale for this approach stems from the biological behavior of glioblastoma itself, in which tumor cells migrate along white matter tracts and infiltrate healthy tissue; therefore, therapies confined to the resection cavity leave significant disease untreated. PoMA's hemisphere-wide mechanism of action is designed specifically to account for this pattern.

Trial Design and Enrollment

The multi-center Phase 2b study (NCT07225621)² is expected to enroll more than 100 newly diagnosed high-grade glioma patients across up to 15 U.S. and European sites. Eligible patients have already undergone resection and standard radio chemotherapy. The trial compares standard of care alone against standard of care plus the investigational PoMA therapy.
The primary endpoint is progression-free survival, with key secondary endpoints including overall survival, safety, and tolerability. With 10 patients enrolled and additional clinical sites continuing to come online, the trial is in active recruitment.

"The Phase 2b trial marks an important step forward in bringing our new therapeutic approach to patients with glioblastoma," said Vijay Agarwal, MD, FAANS, FCNS, chief executive officer of Alpheus Medical, in the press release. "We believe our drug-centered approach has the potential to address the diffuse nature of the disease in ways that localized treatment cannot. With strong early enrollment, we are focused on generating the randomized clinical data to advance this therapy."

Outlook

The results of this trial could carry significant implications for how glioblastoma is managed. Current standard-of-care regimens—including temozolomide chemotherapy and radiation —have seen limited improvement in survival outcomes over the past two decades. A hemisphere-targeting, drug-activated approach such as PoMA, if validated in randomized data, could represent a meaningful shift in how clinicians approach the diffuse biology of the disease.

Alpheus Medical's Phase 2b trial is ongoing, with further enrollment and site activation expected in the coming months.

References

1. Agarwal, V. The promise and potential of porphyrin metabolite activation using sonodynamic therapy for the treatment of glioblastoma. J Neurooncol 177, 45 (2026).
https://doi.org/10.1007/s11060-026-05509-3

2. “Adjuvant Temozolomide ± 5-Aminolevulinic Acid + Low Intensity Diffuse Ultrasound Sonodynamic Therapy System for Newly Diagnosed Glioblastoma” ClinicalTrials.gov.
https://clinicaltrials.gov/study/NCT07225621