William Chou, MD, on Targeting Progranulin With Gene Therapy for Frontotemporal Dementia
The president and chief executive officer of Passage Bio discussed feedback from a recent Type C meeting with the FDA.
“Every patient who gets any modality, there is going to be variability in how high their target engagement is and how high their progranulin gets. If you're on a statin, it may work better for some people, not as well for other people. If, on average, we can get to much higher levels, the variability patient to patient is going to be around a much higher level. Therefore, our odds of being over that threshold of clinical effectiveness go way up. And there is no known toxicity from having high levels of progranulin.”
Passage Bio is set to expand eligibility for its phase 1/2 upliFT-D clinical trial (NCT04747431) evaluating investigational gene therapy PBFT02 in patients with frontotemporal dementia (FTD), following positive FDA feedback in a Type C meeting. The trial will expand 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 has shared data from the first 3 patients treated in upliFT-D last December. These participants 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 and 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 PBFT02, its mechanism, the role of progranulin, and how the therapy may help address unmet needs in people with FTD. He expanded on the progress of the upliFT-D study and emphasized upcoming data that will be presented later in the year.
