The investigational factor VIII (FVIII) gene therapy has been submitted to the FDA.

Patients suffering from Hemophilia A may have an alternative, next-generation treatment some day if Shire’s new gene therapy drug proves to be effective. The company recently filed an investigational new drug (IND) application with the US FDA for its SHP654 (also known as BAX 888) factor VIII (FVIII) gene therapy treatment for the treatment of Hemophilia A.

Hemophilia A is an inherited disease and the most common type of bleeding disorder. It is caused by insufficient clotting factor VIII in the blood. The severity of the disease ranges with the level of factor present, and more than half of patients, most of whom are male, have a severe condition, according to the National Hemophilia Foundation. The disease is complicated by the development of inhibitors which lead to an immune response against clotting factors in approximately one-quarter of these patients.

SHP654 works by achieving a sustained level of expression of FVIII through the use of a recombinant adeno-associated virus serotype 8 (rAAV8) vector that selectively targets the liver. Specifically, a functional copy of FVIII is delivered to the liver to help the body produce its own factor rather than require external delivery. “SHP654 uses the rAAV8 vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient's liver, where FVIII would then be produced and used to manage bleeds. The FVIII expression is further controlled in patients by incorporating the liver-specific transthyretin (TTR) promoter/enhancer,” according to the company’s press release.

Results of preclinical and Phase I studies were promising and led to the IND, according to Shire. If the FDA approves the IND, the company will conduct a global clinical trial with SHP654 to investigate its safety and determine appropriate dosing.