Passage Bio announces initial data from Phase 1/2 trial of PBFT02

Passage Bio announced initial safety and biomarker data from three Cohort 1 patients in the ongoing global Phase 1/2 upliFT-D clinical trial evaluating PBFT02, an adeno-associated virus-delivery gene therapy for the treatment of patients with frontotemporal dementia with granulin mutations. FTD is a form of early onset dementia with no approved disease-modifying therapies. Additionally, the company shared updated strategic priorities aimed at further optimizing its portfolio for the treatment of neurodegenerative conditions. The upliFT-D clinical trial evaluates PBFT02 as a single dose delivered via intra-cisterna magna injection. PBFT02 uses an AAV1 viral vector to deliver a functional copy of the GRN gene encoding PGRN to a patient’s cells. Topline interim results from first three patients in the uplift-D clinical trial: Safety: Dose 1 of PBFT02 was generally well-tolerated in patients 2 and 3, who received an enhanced steroid regimen following protocol amendment. No serious adverse events. All treatment emergent adverse events were mild to moderate in severity. No evidence of clinically significant immune response, hepatotoxicity or safety related imaging abnormalities. Patient 1 received a low level of immunosuppression and experienced two SAEs that were both asymptomatic and consistent with an immune response. Following patient 1, the protocol was amended to increase the steroid regimen for patients 2 and 3. No evidence of dorsal root ganglion toxicity, as measured by nerve conduction studies, and no complications were observed related to ICM administration across any of the three patients. Biomarkers: Dose 1 of PBFT02 treatment resulted in a 3.6 to 6.6-fold increase in CSF PGRN at day 30 relative to baseline. CSF PGRN increased to supraphysiologic levels of 10.7 to 17.3 ng/mL at day 30, exceeding the range found in healthy adult controls of 3.3 to 8.2 ng/mL. CSF PGRN remained at supraphysiologic levels at six months with a concentration of 27.3 ng/mL. Plasma PGRN levels remained below levels found in healthy adult controls through the available follow-up period across all patients.