The results of a phase 1/2, clinical study looking at the safety and efficacy of gene therapy [a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain–deleted human factor VIII (AAV5-hFVIII-SQ) ] to treat 9 adults with severe hemophilia A was recently published in the New England Journal of Medicine (NEJM).  And the results are very promising. Hemophilia A is a heredity bleeding disorder in which persons have a mutation in their genes that code for coagulation factor VIII. Hemophilia A patients are susceptible to excess bruising and bleeding that can be very painful and life threatening.

Current treatment options are limited to transfusions that add factor VIII.

In the NEJM published study, the primary outcome measure was safety and only one serious adverse event (AE) was observed — one person experienced tprogression of chronic arthropathy. All other AEs were mild [increased alanine aminotransferase levels (n=7), arthralgia (n=6), back pain (n=4), increased aspartate aminotransferase level (n=3), fatigue (n=3), and productive cough (n=3).

Regarding the efficacy of the gene therapy, the primary efficacy goal (minimum factor VIII activity level of 5 IU/dL) was achieved in all 7 patients receiving the higher dose of the gene therapy. Further, 6 patients achieved normal levels of factor VIII activity (>50 IU/dL).

Interestingly, of the 6 patients who had received factor VIII prophylaxis prior to the study, their median annualized bleeding rate dropped from 16 events per year to 1 event per year after gene therapy.

The study was sponsored by BioMarin Pharmaceuticals.

For more information about hemophilia A, visit the Canadian Hemophilia Society.