Jun. 23 at 11:20 AM
$PASG Passage Bio reports updated interim data from upliFT-D study of PBFT02
Passage Bio reported updated data from the ongoing Phase 1/2 upliFT-D clinical trial evaluating PBFT02 for the treatment of frontotemporal dementia with granulin mutations and provided program updates and anticipated milestones. Updated interim data from FTD-GRN patients treated with PBFT02: Cerebrospinal Fluid Progranulin: Dose 1 PBFT02 treatment resulted in a robust and durable increase in CSF PGRN expression through 18 months post-treatment.
Dose 1 PBFT02 increased CSF PGRN expression in all patients from below 3 ng/mL at baseline to a mean of 12.4 ng/mL at one month, 19.4 ng/mL at six months, 25.9 ng/mL at 12 months, and 23.8 ng/mL at 18 months. CSF PGRN levels for the first patient treated with Dose 2 PBFT02 increased substantially from 1.5 ng/mL at baseline to 7.6 ng/mL at one month, approaching the upper limit of a healthy adult reference range.
Plasma Neurofilament: Patients who received Dose 1 PBFT02 experienced a reduced annual rate of change of plasma NfL compared to rates observed in natural history studies. Plasma NfL levels increased by 4% on average at 12 months post-treatment compared to an expected increase of 28% and 29% per year in untreated symptomatic FTD-GRN patients based on analysis of the ALLFTD natural history data and published natural history data, respectively. Safety: In five of eight patients, all treatment emergent adverse events were mild to moderate in severity.
Three of eight patients experienced a total of four serious adverse events. As previously disclosed, Patients 1 and 7 experienced a total of three asymptomatic SAEs: venous sinus thrombosis and hepatotoxicity. The first Dose 2 patient experienced the SAE of pulmonary embolism in the setting of a concurrent systemic infection six weeks after receiving PBFT02. The patient responded to treatment with anticoagulants, and the SAE was assessed as possibly related to treatment.No evidence of dorsal root ganglion toxicity, as measured by nerve conduction studies, and no complications during intra cisterna magna administration were observed across any of the eight treated patients.
Study Next Steps: The company plans to amend the upliFT-D clinical trial protocol to introduce a short course of low dose prophylactic anticoagulation, a decision supported by study investigators and the Independent Data Monitoring Committee. The IDMC and U.S. Food and Drug Administration agreed that dosing of Patient 9, who previously enrolled in the study, may proceed with additional safety monitoring in place prior to amendment completion.
Patient 9 will complete Cohort 2, and subsequent patients will be treated as part of Cohort 3, which is now expected to consist of five to 10 patients. In addition, the company intends to amend study inclusion criteria to allow for enrollment of patients who are prodromal or have mild cognitive impairment and exclude patients who are more severely progressed. The company plans to submit the amended protocol to health authorities in early July.
Upon review and acceptance of the amended protocol, the company plans to begin enrollment in Cohort 3 and Cohort 4. Anticipated Milestones: Submit upliFT-D protocol amendment to health authorities in July 2025. Seek regulatory feedback on suspension-based manufacturing process comparability in 2H 2025. Report updated interim safety and biomarker data from Dose 2 in 1H 2026. Seek regulatory feedback on registrational trial design in FTD-GRN in 1H 2026.
