Shire, the leading biotechnology company focused on serving people with rare diseases, has announced the submission of an investigational new drug (IND) application to the US Food and Drug Administration (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, M.D., 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.1 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.1 The FVIII expression is further controlled in patients by incorporating the liver-specific transthyretin (TTR) promoter/enhancer.

The IND filing for SHP654 was based on the results of pre-clinical and phase 1 studies demonstrating the potential utility of this candidate, including the following that will be presented at the International Society on Thrombosis and Haemostasis (ISTH) 26th Biennial Congress in Berlin, Germany.

An IND is a request for FDA authorization to administer an investigational drug to humans. Following the FDA’s acceptance of the IND for SHP654, Shire will study SHP654 in a global multi-center study evaluating safety and examining the SHP654 doses required to boost factor VIII activity levels and affect hemophilic bleeding and will pursue bringing this innovation to markets worldwide.

Shire is developing SHP654 (BAX 888), which includes technology acquired from Chatham Therapeutics, LLC, a spin-out of Asklepios Biopharmaceutical, Inc. SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using a recombinant adeno-associated virus serotype 8 (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.