An experimental gene therapy for Fabry disease has demonstrated significant cost-effectiveness in a small Canadian study, with three of five treated patients able to discontinue expensive enzyme-replacement therapy while maintaining therapeutic benefits five years after treatment.
The early-stage study, published in the Journal of Clinical and Translational Medicine, found that the gene therapy generated $3.7 million in treatment savings against research costs of approximately $4 million, largely funded by the Canadian Institutes of Health Research.
Treatment Approach and Mechanism
The gene therapy utilizes stem cells harvested from patients' bone marrow to deliver replacement copies of the faulty gene responsible for Fabry disease. Dr. Michael West, a co-author and kidney specialist at the Queen Elizabeth II Health Sciences Centre in Halifax, reported that patients continue producing elevated levels of the needed enzymes compared to pre-treatment levels.
"These patients are still producing more of the needed enzymes than they did prior to the gene therapy," said West, who is also a professor at Dalhousie University.
Clinical Outcomes and Safety Profile
Among the five male patients treated between 2016 and 2018, one patient with advanced kidney disease experienced disease stabilization. Notably, none of the participants experienced major cardiovascular or renal events attributable to Fabry disease over the five-year follow-up period.
The treatment demonstrated a favorable safety profile, with only two side effects reported, neither directly related to the gene therapy itself. One patient experienced decreased white blood cell counts due to preparatory chemotherapy used to create space in bone marrow for the modified cells, requiring antibiotic treatment for potential infection. A second patient developed a large leg bruise, also attributed to chemotherapy side effects.
Economic Impact and Current Treatment Burden
The cost-effectiveness becomes particularly significant when considering the burden of conventional enzyme-replacement therapy, which requires bi-weekly treatments lasting approximately two hours each, at an annual cost of $300,000 per patient.
West emphasized the substantial patient burden of existing therapy, noting the frequency and time commitment required for conventional treatment.
Disease Background and Patient Population
Fabry disease is a rare inherited disorder that impairs the body's ability to produce the correct enzyme for breaking down fatty materials, leading to organ damage and shortened lifespans. Symptoms include pain in hands and feet, intestinal problems, and chronic fatigue.
Canada has approximately 540 people with Fabry disease, with about 100 residing in Nova Scotia. The high concentration in Nova Scotia traces back to a French woman who immigrated to Lunenburg during the colonial era, with her descendants carrying the faulty gene through 18 generations.
"Currently, there's some cases in Ontario, there's some in British Columbia, there's some in the U.K., some cases in Florida, but they all originated from here and they share the same mutation," West explained.
Future Research Plans
Recognizing the limitations of the small sample size, researchers plan to expand the study to include 25-30 patients, including women, over a two- to three-year period. West acknowledged that larger-scale studies are necessary before the treatment can become conventional therapy.
Regulatory and Economic Considerations
The ultimate per-patient cost of gene therapy remains undetermined pending regulatory approval from major agencies. West suggested that for rare inherited diseases with small patient populations, government research agencies could develop and own treatments, then charge fees to provide therapies to other national health systems.
The 72-year-old physician noted that while other gene therapy applications have sometimes resulted in severe side effects including cancer development, the Fabry disease treatment has shown a more favorable risk profile to date.
