Margaret Ragni, MD: Liver Abnormalities in Hemophilia A Gene Therapy Require Close Monitoring

Ragni explained the factor VIII (FVIII) gene therapy Roctavian has shown remarkable results, including an 80% reduction in annualized bleed rate and ~98% reduction in clotting factor use, potentially setting a new standard for comparison with other therapies for hemophilia A.

Quality of life studies have indicated some improvement, particularly in the second year of treatment. However, close monitoring is crucial for those living with the rare disease, especially during the first year of receiving the therapy, as liver abnormalities may occur in approximately 80% of patients, possibly leading to loss of the gene vector if not promptly addressed with steroids.

“​​If your liver tests become abnormal, we need to know that rather quickly so that we can intervene, and here's why–of you have liver abnormalities, and the liver is suffering some damage from this vector, if you don't start the steroids quickly, you may end up losing the vector gene that has been given and you have no more expression,” Ragni said. “So, it's very important to have excellent follow up with your physicians not just in that first year, but even following that.”

Ragni emphasized the importance of shared decision-making with patients and involving them and their families in discussions regarding treatment options and providing comprehensive information. Looking ahead, ongoing research is focused on improving liver health, reducing side effects, and exploring the therapy's suitability for children and adults with AAV antibodies.

“I consider myself the conduit to provide the information (the patients) really need,” she explained, “and to go along with them step-by-step as the future unfolds to make sure they're aware of anything new that we find out, and involve the family because that's a very important aspect of managing this disease.”

Research is also aiming to refine the gene vector combinations as an attempt to minimize liver toxicity and explore the use of smaller gene sizes, enhancing efficacy. Exciting developments in mRNA and gene editing therapies are expected to bring even safer and more effective treatments in the future, she shared.