Podcast recap: Chris Hopkins on developing a one-time cell therapy for Fabry disease

On this episode of The Genetics Podcast, Patrick spoke with Chris Hopkins, CEO of Glafabra Therapeutics, a company developing a one-time autologous cell therapy for Fabry disease. The therapy is designed to provide durable enzyme replacement without the limitations of current treatments and may serve as a platform for other lysosomal storage disorders.

Rethinking Fabry treatment

Fabry disease leads to progressive cardiac, renal, and central nervous system complications due to a missing enzyme. The current standard of care is enzyme replacement therapy (ERT), and it requires patients to receive biweekly infusions for life. While ERT helps manage symptoms, it is burdensome and does not effectively address neurological manifestations.

When Chris learned of a Canadian academic study showing long-term benefit from an early cell therapy approach, he saw an opportunity to revive and modernize the program. Glafabra was founded to reposition this shelved asset and move it back into the clinic.

How the therapy works

The company’s approach involves collecting a patient’s hematopoietic stem cells, using a lentiviral vector to insert a functional copy of the missing gene, and reinfusing the modified cells after mild, outpatient conditioning. These cells secrete the missing enzyme, which can be taken up by neighboring tissues.

Because the therapy uses the patient’s own cells and removes viral capsid proteins during processing, there is minimal immune response. This allows for repeat dosing, addressing one of the main limitations of AAV-based gene therapies, which typically cannot be redosed due to immune sensitization.

Early clinical evidence

In the Canadian study, five Fabry patients discontinued ERT and received the autologous cell therapy. Biomarker analysis showed a 41% rebound in toxic metabolites during the ERT washout period, followed by a 48% reduction after treatment.

Four of the five patients have maintained durable enzyme activity and metabolic control for over seven years, with one showing waning efficacy at around four years, demonstrating both the durability of the effect and the feasibility of redosing.

Patients also reported improvements in neurological symptoms, suggesting that the therapy may help address central nervous system effects that ERT cannot reach.

Comparison with other modalities

Chris contrasted Glafabra’s approach with other genetic therapies. AAV gene therapy can offer long-term expression but cannot be safely repeated, and some patients lose efficacy over time. Gene editing approaches like CRISPR are effective for dominant gain-of-function mutations but require harsh procedures to eliminate the patient’s own hematopoietic stem cells. 

Fabry and other loss-of-function disorders only need partial enzyme restoration. Glafabra’s mild, sub-myeloablative “augmentation” procedure enables durable benefit with a more tolerable safety profile.

A platform for lysosomal disorders

Chris emphasized that the technology could extend beyond Fabry. Because lysosomal enzymes are secreted and reabsorbed by surrounding cells, this same platform could be applied to many of the 48 known lysosomal storage diseases simply by swapping the transgene. This opens the door to regulatory efficiencies and accelerated development for multiple indications.

Challenges in diagnosis and access

Chris noted that Fabry disease is widely underdiagnosed. Global registry data suggest around 10,000 known patients, yet population-scale sequencing indicates the true prevalence may be closer to 1 in 2,000–4,000 individuals. He sees a major opportunity to improve early detection through newborn screening once more durable, accessible treatments are available.

Path to the clinic

Glafabra is pursuing orphan drug designation and preparing for an FDA INTERACT meeting. Chris outlined a phased plan:

• Approximately $0.5 million to secure orphan status and regulatory alignment
• Around $4 million for CMC development to open an IND
• About $10 million to reach initial efficacy data
• Roughly $50 million to advance a second program and demonstrate platform potential

Because Fabry is a rare disease with well-characterized biomarkers, Chris expects that modest patient numbers could be sufficient for an initial efficacy readout under orphan and accelerated approval frameworks.

Cost, scalability, and the road ahead

While autologous manufacturing is complex, the economics compare favorably to lifelong ERT, which can cost $500,000–$1 million per patient annually. Chris expects further cost reductions through process automation, AI-driven manufacturing optimization, and, in the long term, low-immunogenicity allogeneic sources.

He sees the broader field of cell and gene therapy maturing toward greater efficiency and accessibility, much as monoclonal antibodies did a generation ago.

Listen to the full episode below.