FDA authorizes direct CSF injection of DeltaRex-G for leptomeningeal disease

FDA CBER has authorized an intraventricular injection of DNG64-CAR-V (DeltaRex-G) directly into cerebrospinal fluid for a patient with refractory glioblastoma that has spread to the brain and spinal fluid. The decision could broaden access to an off-the-shelf gene therapy platform being studied for brain tumors, leukemia, lymphoma and other cancers that metastasize to the brain.

Why it matters: - The FDA authorization opens a new delivery route for DNG64-CAR-V, a tumor-targeted gene therapy, in a patient with leptomeningeal disease. - The approval could matter for patients with cancers that spread to the brain or cerebrospinal fluid, including glioblastoma, osteosarcoma, melanoma, lung cancer, breast cancer, leukemia and lymphoma. - The decision also adds momentum to an off-the-shelf therapy platform already being used through expanded access.

What happened: - Aveni Foundation announced that FDA CBER authorized injection of DNG64-CAR-V (DeltaRex-G) directly into cerebrospinal fluid through an Ommaya reservoir. - The authorization applies to a patient with refractory glioblastoma that has spread to the cerebrospinal fluid and the membranes covering the brain and spinal cord. - The patient case is tied to IND#32087.

The details: - DNG64-CAR-V is described as an off-the-shelf, injectable, replication-incompetent chimeric amphotropic RNA vector. - The therapy encodes a Cyclin G1/CCNG1 inhibitor construct. - The platform is designed to kill cancer cells, neoangiogenic cells and cancer-associated fibroblasts in the tumor microenvironment. - By reducing stroma, DNG64-CAR-V is intended to improve entry of chemo and immunotherapy drugs into the tumor microenvironment. - Drs. Erlinda Maria Gordon and Frederick L. Hall created and reduced to practice the targeted gene delivery system at USC Keck School of Medicine in Los Angeles. - Dr. Santosh Kesari called the product the first tumor-targeted gene therapy product authorized by FDA CBER for direct delivery into the CSF. - Dr. Sant P. Chawla said the emergency use authorization could help patients whose cancers have spread to the brain. - Dr. James H. Flint and Dr. Erlinda M. Gordon said the authorization honors Will Roberts, a young man from Ralph, Alabama, who sought access to DeltaRex-G for osteosarcoma that had spread to his brain. - The therapy has been used intravenously in phase I/II studies for sarcoma, pancreatic cancer and breast cancer. - The therapy also has been studied in a phase II clinical trial for osteosarcoma that had failed standard chemotherapy. - The release cites long-term survivors from 10 to 18 years after treatment and says no delayed adverse events were reported. - DNG64-CAR-V is available through an expanded access program sponsored by Aveni Foundation under NCT04091295.

Between the lines: - The authorization suggests regulators are willing to consider direct CSF delivery for a gene therapy aimed at disease that is difficult to reach with standard treatments. - The announcement also highlights how a single compassionate-use style case can become a broader access point for a platform therapy. - The therapy’s prior use in blood vessel and solid tumor settings is being used to support interest in treating cancers that have spread to the central nervous system.

What's next: - Aveni Foundation directs interested parties to its website, Sarcoma Oncology Center resources and Dr. Gordon for more information about the program. - The expanded access pathway could become the main route for additional patients while the therapy continues to be positioned across multiple cancer types. - The release also points to donation and contact channels for further support and inquiries.

The bottom line: - FDA’s authorization gives DeltaRex-G a new, highly targeted route into the cerebrospinal fluid, potentially widening options for patients with cancers that have spread to the brain and spinal lining.