Passage Bio Closes FTD Gene Therapy Trial to New Patients After FDA Demands Randomized Study

The company said May 15 it will no longer enroll patients in its progranulin gene therapy trial, a month after the FDA told it a placebo-controlled, randomized trial would be required to seek approval for FTD-GRN.

Passage Bio announced on May 15, 2026 that it is closing its upliFT-D clinical trial to new enrollment, ending recruitment into the open-label study of PBFT02, an experimental gene therapy for frontotemporal dementia caused by mutations in the progranulin (GRN) gene. The move follows an April 20, 2026 disclosure by the company that the Food and Drug Administration, after a Type C meeting, had told Passage Bio that a randomized, placebo-controlled trial, not the single-arm design used in upliFT-D since 2021, would be required for a registrational filing in FTD-GRN.

In its April 20 statement, Passage Bio said such a trial "poses substantial ethical concerns for patients and their families" in addition to logistical and financial challenges, a reference to the fact that PBFT02 is delivered by a one-time neurosurgical injection into the cisterna magna at the base of the skull, making a sham-surgery placebo arm difficult to justify in a small, genetically defined patient population. The company said at the time it was evaluating potential next steps for PBFT02 in both FTD-GRN and a related cohort of patients with C9orf72 mutations, and had begun a broader review of strategic alternatives for the company.

The interim data Passage Bio had been citing came from an open-label trial with no concurrent control group: the April update reported that treated patients showed less brain volume loss on MRI and more stable levels of a nerve-damage marker in blood, plasma neurofilament light, compared with natural-history data drawn from untreated patients rather than from a randomized comparison group within the same study. Patient advocacy groups tracking the program, including the Association for Frontotemporal Degeneration and the Bluefield Project's Progranulin Navigator resource, reported the closure to their communities the same day, noting that Passage Bio's release called the news "deeply disappointing" for families who had followed the program.

Passage Bio has not said whether or how it might design a randomized, placebo-controlled trial for PBFT02, or whether another sponsor might take up the program under its ongoing review of strategic alternatives. For now, the upliFT-D trial remains closed to new participants, and no registrational pathway for the therapy has been agreed with regulators.