Gene therapy shows promise as glioma treatment in early study
Small trial finds survival benefit for people with recurrent, malignant brain cancer
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NeuExcell Therapeutics‘ investigational gene therapy, NXL-004, showed a potential survival benefit in a small group of people with recurrent malignant glioma in an early clinical trial.
While people with this type of brain cancer don’t usually survive more than about nine months after their diagnosis, median survival in treated patients was over a year.
Trial investigator Yulun Huang, a physician at the Fourth Affiliated Hospital of Soochow University in China, was scheduled to present the data in a talk at the American Society of Clinical Oncology’s annual meeting, held May 29-June 2 in Chicago.
The program’s selection for presentation “underscores the potential of our … platform to address significant unmet needs in recurrent malignant glioma and potentially other devastating neurological diseases,” Gong Chen, PhD, founder and chief scientific officer of NeuExcell, said in a company press release.
Malignant gliomas are cancerous brain tumors that arise from nerve support cells called glia. They are typically aggressive and fast-growing, easily infiltrating nearby healthy brain tissue.
No cure for hard-to-treat cancer
Malignant glioma is one of the most difficult cancers to treat, and commonly recurs, or returns, after initial treatment. No therapies have demonstrated a clear survival benefit in clinical trials for people with recurrent malignant glioma, according to NeuExcell.
Most glioma treatments focus on removing or killing tumor cells, but NXL-004 takes a somewhat different approach. It is a cell conversion therapy designed to reprogram cancer cells into healthy brain cells.
The treatment aims to increase levels of NeuroD1, a transcription factor protein that activates genes promoting nerve cell growth and survival. Turning on those genes in cancerous cells may help convert the abnormal, rapidly growing glial cells into healthy, nerve-like cells. The therapy may also promote tumor cell death.
To increase NeuroD1 levels in tumor cells, NXL-004 delivers the gene responsible for producing it. The gene is packaged into a viral vector called an adeno-associated virus (AAV), which helps it be taken up by cells.
The first in-human trial (ChiCTR2400080362) was designed as an exploratory study to evaluate the safety and preliminary efficacy of NXL-004 and to determine an optimal dose range for future studies.
It enrolled 11 adults with malignant glioma that had returned or progressed after initial treatment. Participants had a median age of 48, and most (81.8%) were male.
All participants had a type of glioma called an astrocytoma, which arises from cells called astrocytes. In all cases, the cancer was Grade 4, the most aggressive form of glioma, in which the cancer rapidly invades brain tissue.
Ten participants received surgery to remove as much of the brain tumor as possible, followed by the injection of NXL-004 into the cavities of the brain. One participant did not have tumor removal surgery, and the medication was injected directly into the tumor.
NeuExcell said the median overall survival time was 13.2 months, with 77.9% of participants surviving for at least one year. Historically, survival for recurrent malignant glioma is six to nine months after diagnosis, according to the company.
All five patients who received a high dose of the therapy were still alive at the time of the report. Four of them had survived for more than a year.
One person who received high-dose treatment achieved a complete treatment response (where there are no remaining signs of the tumor) and has remained alive without signs of cancer progression for over a year. Another person achieved durable stable disease, meaning their tumor remained about the same size, and has remained alive without cancer progression for 11 months.
No medication-related serious adverse events occurred. Any treatment-related side effects were mild or moderate, with the most common being fever and headache.
“This study represents the first clinical evaluation of an AAV-NeuroD1 based gene therapy for glioma,” Huang said. “The findings provide encouraging evidence supporting both the safety and therapeutic potential of this novel approach.”
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