Passage Bio’s Trial Shows 64% Brain Atrophy Reduction, FDA Demands RCT
Passage Bio’s Phase 1/2 upliFT-D trial of PBFT02 in FTD-GRN showed a 64% reduction in whole brain atrophy and a 54% decrease in frontotemporal cortex atrophy at 12 months versus controls. Plasma NfL stabilized with a 1.0 pg/mL drop versus a 13.5 pg/mL rise, while CSF progranulin exceeded 22 ng/mL.
1. Interim Biomarker Improvements
PBFT02-treated global CDR 1 patients experienced a 64% reduction in whole brain atrophy and a 54% reduction in frontotemporal cortex atrophy at 12 months compared to natural history controls. Plasma neurofilament levels fell by 1.0 pg/mL at 12 months versus a 13.5 pg/mL rise in untreated patients, and CSF progranulin exceeded 22 ng/mL for both Dose 1 and Dose 2 cohorts.
2. FDA Regulatory Guidance
Feedback from a Type C meeting with the FDA indicated that a randomized controlled registrational trial will be required for PBFT02 in FTD-GRN, rejecting a single-arm design despite robust natural history data. This decision introduces significant logistical, ethical, and financial challenges for late-stage development.
3. Strategic Review and Financial Advisory
Passage Bio has engaged Wedbush PacGrow as financial advisor and initiated a strategic review process to maximize shareholder value. The company is evaluating potential next steps for PBFT02’s clinical development and broader corporate options in light of the FDA’s guidance.
4. Safety Profile
PBFT02 continues to be generally well-tolerated with no new treatment-related serious adverse events reported. Previously, two Dose 1 patients experienced asymptomatic venous sinus thrombosis and hepatotoxicity, with no evidence of dorsal root ganglion toxicity or complications from intracisterna magna administration.