Margaret Ragni, MD: Roctavian Shows 80% Bleed Reduction Supporting FDA Approval

The US Food and Drug Administration (FDA) has approved Roctavian gene therapy for the treatment of severe hemophilia A in adults. This marks a significant milestone as Roctavian becomes the first gene therapy approved for the rare disease in the US.

"This is quite an amazing approval for the simple reason that hemophilia, in particular, hemophilia A is a very severe disease," medical director of the Hemophilia Center of Western Pennsylvania Margaret Ragni, MD, MPH, said in an interview in HCPLive.

The approval of Roctavian is based on the results from the GENEr8-1 study, which followed patients for 3 years, making it the largest and longest study of gene therapy for hemophilia conducted so far.

"(With Roctavian) there is a marked reduction in bleeds–as much as 80%, fewer bleeds, there is a 98% reduction in clotting factor use," she explained. "This is significant."

The FDA reported the mean ABR for spontaneous bleeds was 0.5 bleeds per year, and for joint bleeds, it was 0.6 bleeds per year among the patients who received Roctavian. In comparison, their baseline rates while on routine FVIII prophylaxis were 2.3 bleeds per year for spontaneous bleeds and 3.1 bleeds per year for joint bleeds.

However exciting the agency's decision is, Ragni acknowledged "one must balance it with the potential for complications," as about 80% of patients who receive the gene therapy develop liver abnormalities which may be related to putting a gene vector into the hepatocyte, sometimes referred to as "ER stress".

"There is a transient liver abnormality seen in over 80% (of patients) that requires steroids," she said. "There are some complications of using steroids, but this is short term, so it should not be a major issue but for a number of the patients in the trial they required treatment for over a year."

Most study participants continued to respond positively to Roctavian beyond the 3-year mark without requiring regular prophylaxis supplementation, according to the study. Developing company BioMarin plans to conduct an extension study to assess the long-term effects of treatment, monitoring all clinical trial participants for up to 15 years.

Ragni is also a professor of medicine and clinical translational science, in addition to her role as the medical director of the Hemophilia Center of Western Pennsylvania, and a member of the American Society of Hematology (ASH).