Biotechnology firm Passage Bio recently provided updated interim data from its phase 1/2 clinical trial for its gene replacement therapy targeting FTD-GRN.

Experimental Therapy Continues to Show Improved Progranulin Levels

In FTD caused by an inherited GRN genetic variant, production of the neuroprotective protein progranulin is suppressed, contributing to the buildup of TDP-43, a key driver of FTD pathology and symptoms. Passage Bio’s experimental therapy PBFT02 seeks to remedy the suppression of progranulin production by re-introducing a working copy of the GRN gene using an engineered virus known as a “vector.”

Passage Bio announced that PBFT02 continues demonstrating “robust, durable elevation” of progranulin levels in cerebrospinal fluid. Preliminary data from the first participant in the second cohort, which was not available when the company released interim data in January, is also now available.

Passage Bio’s clinical trial includes multiple groups of people, or cohorts, each receiving different doses of PBFT02, to help them determine optimal dosage. Participants in cohorts 1 and 2 all experienced substantial increases in their progranulin levels. In addition, data from cohort 1 demonstrated a reduced rate of change of NfL, compared to what is seen in natural history studies where there is no intervention (learn more about natural history data and NfL on AFTD’s YouTube channel).

While the results are promising, serious adverse reactions (SAEs) occurred in three of eight treated people in the study. The SAEs were related to blood clot formation and were assessed as possibly related to treatment. The events were addressed by a course of anticoagulant medication; the three people responded positively to the treatment.

Trial Protocol to be Updated Before Third and Fourth Cohorts

Passage Bio plans to submit an amended trial protocol to health authorities with several changes, including adding a course of prophylactic anticoagulants, a preventative measure commonly used to reduce the risk of blood clot formation in people at increased risk. The new protocol would also allow enrollment of people earlier in their FTD disease course, including those who are prodromal or have mild cognitive impairment.

The updated trial protocol will be in place for Cohorts 3 and 4; the latter will focus on FTD caused by C9orf72 variants. Passage Bio received positive feedback from the U.S. Food and Drug Administration last year regarding its expansion to C9orf72.

“We continue to refine our understanding of the safety profile of PBFT02 and believe that our planned changes to the study protocol will further optimize the benefit-risk profile of the program,” said Will Chou, MD, president and chief executive officer of Passage Bio. “We remain on track to engage with regulatory authorities on a future registrational trial design in the first half of 2026.”

The upliFT-D clinical trial recruits people with a confirmed pathogenic mutation of GRN or C9orf72 with a clinical diagnosis of FTD. To learn more about participating in upliFT-D, visit the study’s clinicaltrials.gov page or Passage Bio’s trial webpage. If you have questions or concerns about participation, contact AFTD’s HelpLine at 1-866-507-7222 or info@theaftd.org.

Are you interested in participating in other studies for FTD? Sign up at the FTD Disorders Registry to learn of recruiting studies when they match your interests. You may also be eligible for the online Registry Research Study to share insights about diagnosis, family history, lived experience, genetic testing, medical records, and more. Numbers have power. The more participants, the more we can help researchers design studies for which people are ready and willing to participate.