William Chou, MD, on Expanding Frontotemporal Dementia Gene Therapy to Both GRN and C9orf72 Mutations

“The goal of the meeting was to expand our current trial from just FTD-GRN patients to also include frontotemporal dementia patients who have a different mutation. They have a mutation called the C9orf72 mutation, and this would be the first time that we've seen that a development program has used a gene therapy beyond just the population that is deficient in that 1 gene. And the reason that we feel very excited about this approach is there is good preclinical evidence that raising progranulin can ameliorate a pathology called TDP-43 pathology.”

The FDA has given positive feedback to Passage Bio in a Type C meeting regarding the company’s plans to expand eligibility for its phase 1/2 upliFT-D clinical trial (NCT04747431) evaluating investigational gene therapy PBFT02 in patients with frontotemporal dementia (FTD). The FDA supported the trial’s expansion from including patients with FTD with GRN mutations (FTD-GRN) to also include patients with FTD with mutations in the C9orf72 gene (FTD-C9orf72).¹

Passage shared initial data from upliFT-D last December from 3 patients in the study’s first cohort that experienced a 3.6 to 6.6-fold increase in cerebrospinal fluid (CSF) PGRN over baseline at 30 days posttreatment to reach 10.7 to 17.3 ng/mL. These participants sustained their supraphysiologic PGRN levels in the CSF at 6 months after receiving the gene therapy, compared with 61 healthy adults used as a control, whose CSF PRGN was measured at 3.3 to 8.2 ng/mL.²

CGTLive spoke with William Chou, MD, president and chief executive officer of Passage Bio, to learn more about the feedback from the Type C meeting and actions the company is taking in response to the feedback. He detailed the planned expansion from patients with FTD-GRN to also FTD-C9orf72 and the preclinical data that Passage has seen to support this move.

REFERENCES

1. Passage Bio announces positive feedback from FDA on expansion of upliFT-D trial of PBFT02 to include FTD-C9orf72 patients. News release. Passage Bio, Inc. July 16, 2024. Accessed July 19, 2024. https://www.passagebio.com/investors-and-news/press-releases-and-statements/news-details/2024/Passage-Bio-Announces-Positive-Feedback-from-FDA-on-Expansion-of-upliFT-D-Trial-of-PBFT02-to-Include-FTD-C9orf72-Patients/default.aspx
2. Passage Bio announces promising initial data from phase 1/2 clinical trial of PBFT02 in FTD-GRN and updated strategic priorities. News release. Passage Bio, Inc. December 20, 2023. Accessed July 19, 2024. https://www.passagebio.com/investors-and-news/press-releases-and-statements/news-details/2023/Passage-Bio-Announces-Promising-Initial-Data-From-Phase-12-Clinical-Trial-of-PBFT02-in-FTD-GRN-and-Updated-Strategic-Priorities/default.aspx