SHP654 aims to deliver sustained protection against bleeds for patients with hemophilia A.

Shire has submitted an investigational new drug (IND) application to the FDA for SHP654, also designated as BAX 888, an investigational factor VIII (FVIII) gene therapy for the treatment of hemophilia A. SHP654 aims to protect hemophilia A patients against bleeds through the delivery of a long-term, constant level of factor expression. The IND filing for SHP654 represents the latest step forward for Shire’s gene therapy program, which shows promise for both hemophilia A and B populations.

"Shire is leveraging decades of scientific leadership in hemophilia to advance research in gene therapy for this community," said Paul Monahan, Senior Medical Director, Gene Therapy, Shire. "Drawing from our rich heritage, Shire is well equipped to sustainably support the development of gene therapies that aim to advance current standards of care and minimize the burden of this disease. SHP654 uses a proprietary technology platform designed to produce sustained levels of factor similar to the natural mechanisms of the body. Our goal with gene therapy for hemophilia is to uphold the highest standards for safety and efficacy."

Shire’s gene therapy program for hemophilia A uses a recombinant adeno-associated virus serotype 8 (rAAV8) vector, which selectively targets the liver. It involves the delivery of a functional copy of FVIII to the body’s liver to enable its own production of FVIII, rather than relying on a factor-based treatment. 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.