Irish-headquartered Shire has submitted 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 to treat haemophilia A.
SHP654 helps protect patients with haemophilia A against bleeds through the delivery of a long-term, constant level of factor expression.
Haemophilia A is the most common type of haemophilia and a rare bleeding disorder that causes unusual bleeding due to lack of clotting FVIII in the blood.
Also known as an anti-haemophilic factor (AHF), FVIII is an important protein that helps in blood clotting.
Shire gene therapy senior medical director Dr Paul Monahan said: “Shire is leveraging decades of scientific leadership in haemophilia to advance research in gene therapy for this community.
“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 minimise 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.”
The company’s gene therapy programme for haemophilia 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 instead of relying on a factor-based treatment.
Shire’s SHP654 therapy uses the rAAV8 vector to deliver a codon-optimised, B-domain deleted FVIII (BDD-FVIII) particularly to the patient’s liver, where FVIII would then be generated and used to manage bleeds.
The FVIII expression is further controlled in patients by using the liver-specific transthyretin (TTR) promoter / enhancer.
The company filed the IND application for SHP654 based on the results of pre-clinical and Phase I studies highlighting the potential utility of the candidate.