Shire submits IND application for haemophilia treatment

Breakthrough status for Roche’s haemophilia A treatment
Credit: wacomka

Shire has submitted an investigational new drug (IND) application to the US Food and Drug Administration for SHP654, an investigational factor VIII (FVIII) gene therapy for the treatment of haemophilia A.

SHP654 aims to protect haemophilia 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 haemophilia A and B populations.

Paul Monahan, M.D., Senior Medical Director, Gene Therapy, Shire, said: “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 haemophilia is to uphold the highest standards for safety and efficacy.”

Shire’s gene therapy program 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, rather than relying on a factor-based treatment.

SHP654 uses the rAAV8 vector to deliver a codon-optimised, 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.

The IND filing for SHP654 was based on the results of pre-clinical and phase 1 studies demonstrating the potential utility of this candidate.