PASG - Passage Bio Announces Promising Initial Data From Phase 1/2 Clinical Trial of PBFT02 in FTD-GRN and Updated Strategic Priorities | Benzinga
- Dose 1 of PBFT02 achieved supraphysiologic CSF progranulin levels in each of the first three treated patients at 30 days after treatment
- Elevated progranulin levels were sustained at up to six months post-treatment
- Dose 1 of PBFT02 was generally well-tolerated in patients who received an enhanced steroid regimen for immunosuppression
- Pipeline to focus on continued advancement of PBFT02 in FTD-GRN and explore PBFT02 in multiple additional adult neurodegenerative diseases
- Pursuing potential partnership opportunities for clinical-stage pediatric lysosomal storage disease programs including GM1 gangliosidosis
- Management to host a webcast presentation to review interim FTD data today at 8:30 a.m. ET
PHILADELPHIA, Dec. 20, 2023 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ:PASG), a clinical-stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases, today 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 (AAV)-delivery gene therapy for the treatment of patients with frontotemporal dementia (FTD) with granulin (GRN) 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.
"We are proud to announce initial clinical data from our upliFT-D clinical trial, which showcases the ability of PBFT02 to elevate CSF progranulin to supraphysiologic levels at the lowest tested dose, Dose 1, up to six months post-treatment. We believe these data, surpassing our expectations based on preclinical non-human primate models, validate the compelling potential of PBFT02 to address progranulin deficiency—a key driver of disease progression in individuals with FTD-GRN," said Mark Forman, M.D., Ph.D., chief medical officer at Passage Bio.
FTD is one of the more common causes of early-onset dementia. In approximately 5 to 10 percent of individuals with FTD–approximately 18,000 individuals in the United States and Europe—the disease occurs because of mutations in the GRN gene, causing a deficiency of progranulin (PGRN). PGRN is a complex and highly conserved protein thought to have multiple roles in cell biology, development and inflammation. Emerging evidence suggests that PGRN deficiency may contribute to lysosomal dysfunction.
The upliFT-D clinical trial evaluates PBFT02 as a single dose delivered via intra-cisterna magna (ICM) 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 (patient follow-up up to six months)
- 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 (SAEs).
- All treatment emergent adverse events (AEs) 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 (60 mg oral prednisone for 60 days) 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 (1,000 mg IV methylprednisolone on days 1-3 followed by 60 mg oral prednisone through day 60) for patients 2 and 3.
- No evidence of dorsal root ganglion (DRG) toxicity, as measured ...