Passage Bio Receives FDA Approval to Expand upliFT-D Trial to FTD-C9orf72 Patients

Passage Bio, Inc., a clinical-stage company specializing in genetic medicines for neurodegenerative diseases, recently obtained positive feedback from the U.S. Food and Drug Administration (FDA) regarding its proposal to broaden the upliFT-D trial to evaluate PBFT02 in patients with frontotemporal dementia (FTD) linked to C9orf72 gene mutations. Drawing from compelling preclinical findings and encouraging safety and progranulin expression data from the initial cohort of FTD-GRN patients treated with PBFT02, the FDA agreed to the proposed trial expansion.

Dr. Will Chou, President and CEO of Passage Bio, emphasized the importance of FDA approval in extending the upliFT-D protocol to include FTD-C9orf72 patients. He highlighted the scarcity of clinical trials for this patient group and expressed confidence that PBFT02 could meet a significant unmet medical need, offering new hope to these patients. Chou added that the company is eager to further the clinical development of PBFT02, building on the promising data observed so far in the upliFT-D trial.

FTD-C9orf72 affects an estimated 21,000 people in the United States and Europe. Like FTD-GRN, FTD-C9orf72 is characterized by the abnormal accumulation of transactive response DNA binding protein 43 (TDP-43) in the cytoplasm of neurons, leading to neuronal dysfunction and degeneration. External preclinical studies have shown that increasing progranulin (PGRN) levels can reduce TDP-43 pathology and slow neurodegeneration.

Passage Bio plans to promptly submit the revised trial protocol to health authorities and ethics committees, aiming to begin dosing FTD-C9orf72 patients in the first half of 2025.

PBFT02 has been granted Fast Track and Orphan Drug designations by the FDA and Orphan designation by the European Commission. The therapy employs an AAV1 viral vector to deliver a functional GRN gene through intracerebroventricular (ICM) administration. This approach aims to elevate PGRN levels in the central nervous system (CNS), potentially altering the course of neurodegenerative diseases. Preclinical studies have shown broad transduction across the brain, including high transduction of ependymal cells, and have demonstrated significant increases in cerebrospinal fluid (CSF) PGRN concentrations. Clinical data so far has confirmed robust CSF PGRN levels.

Passage Bio is dedicated to developing innovative, one-time therapies to address the root causes of neurodegenerative diseases. Through advancements in genetic medicine, the company aims to improve the lives of patients suffering from these debilitating conditions. Their lead product candidate, PBFT02, is designed to treat neurodegenerative disorders, including frontotemporal dementia, by increasing progranulin levels to restore lysosomal function and slow disease progression.

In summary, Passage Bio's recent FDA feedback supports the company's efforts to expand its upliFT-D trial to include a new patient population, potentially offering a much-needed treatment option for those with FTD linked to C9orf72 gene mutations. As the company prepares to initiate dosing of FTD-C9orf72 patients, it continues to build on promising preclinical and clinical data, with the hope of bringing innovative therapies to patients with neurodegenerative diseases.