April 20, 2026 —
Passage Bio announced updated interim results from its ongoing Phase 1/2 upliFT-D clinical trial evaluating PBFT02, an AAV1-based gene therapy for frontotemporal dementia caused by granulin mutations (FTD-GRN). The data suggest that PBFT02 may slow neurodegeneration, as evidenced by improvements in key disease progression biomarkers, including reduced brain atrophy and stabilization of plasma neurofilament light chain (NfL) levels when compared to natural history data.
PBFT02 is designed to deliver a functional GRN gene using an adeno-associated virus serotype 1 (AAV1) vector, administered via a one-time intracisterna magna injection to target the central nervous system. The therapy aims to restore progranulin (PGRN) levels, a protein deficient in patients with GRN mutations and implicated in disease progression. In treated patients, the therapy demonstrated robust and sustained increases in cerebrospinal fluid PGRN levels, with both high and lower dose cohorts achieving meaningful expression.
Clinical outcomes showed that patients in earlier stages of disease progression experienced significant reductions in brain atrophy. Specifically, whole brain atrophy was reduced by 64% and frontotemporal cortex atrophy by 54% at 12 months compared to matched natural history cohorts. Additionally, plasma NfL levels—a biomarker associated with neurodegeneration—remained stable in treated patients, contrasting with increases typically observed in untreated populations.
The therapy was generally well tolerated, with no new treatment-related serious adverse events reported. Previously observed adverse events included asymptomatic venous sinus thrombosis and hepatotoxicity in a small number of patients. No evidence of dorsal root ganglion toxicity or complications related to the delivery method has been observed to date.
Alongside the clinical update, Passage Bio shared feedback from a recent Type C meeting with the U.S. Food and Drug Administration, which indicated that a randomized controlled trial will be required for registrational approval of PBFT02 in FTD-GRN. This represents a shift from potential single-arm study approaches and introduces additional ethical, logistical, and financial considerations for a rare and rapidly progressive disease.
In parallel, the company announced it has initiated a strategic review process, engaging Wedbush PacGrow as a financial advisor to explore options aimed at maximizing shareholder value. The future development pathway for PBFT02 remains under evaluation as the company considers regulatory requirements and broader strategic priorities.
