Shire’s Experimental Gene Therapy Delivery Strategies Show Potential for Hemophilia A and B

Shire’s Experimental Gene Therapy Delivery Strategies Show Potential for Hemophilia A and B

Shire is developing a potential new strategy to improve the effectiveness of genetic delivery of clotting factor VIII (FVIII) for the treatment of patients with hemophilia A, and clotting factor IX (FIX) for patients with hemophilia B.

The most recent findings on these new therapeutic strategies and the latest advances on the company’s pipeline will be the subject of oral and poster presentations at the 26th Biennial International Society on Thrombosis and Haemostasis Congress July 8-13 in Berlin, Germany.

All the abstracts of the presentations can be consulted in the book of abstracts of the meeting.

“As the global leader in rare hematology with over 70 years of expertise, Shire is proud to showcase the depth of our hemophilia portfolio and the latest data reinforcing the proven safety and efficacy of our products,” Bruce Ewenstein, an MD and PhD, the vice president of clinical development for hematology at Shire, said in a press release.

The goal of gene therapy in hemophilia is to overcome the lack of clotting factors caused by genetic mutations. The delivery of a correct form of the defective gene has the potential to alleviate bleeding episodes, transforming severe cases of hemophilia into mild or even normal blood clotting events.

Clinical trial results have demonstrated that genetic delivery of FVIII can restore to a normal range the levels of missing clotting factor in hemophilia A. However, the available delivery methods have production restraints, and have demonstrated associated toxicity effects.

Shire is now developing new delivery strategies based on more efficient and liver-specific delivery vectors, combined with a specific FVIII genetic sequence.

In the study titled “Development of SHP654, a highly efficient AAV8-based BDD-FVIII gene therapy vector for treatment of hemophilia A,” researchers present the potential new gene therapy SHP654.

This formulation was shown to promote 74-fold higher levels of FVIII compared to the normal clotting factor gene sequence. In addition, the production of this new product was very high while ensuring the desired stability of the vector.

In second study, titled “Integration site analysis in mice demonstrates excellent biosafety profile of a recombinant (r) FVIII adeno-associated virus (AAV8) gene therapy product,” the researchers confirm in preclinical mouse models that the new SHP654 does not present any potential harmful effect resulting from genetic integration of the new gene in the genome – the complete genetic information in a cell.

Researchers did not detect any treatment-associated liver cell growth that could potentially be associated with human hepatocellular carcinoma.

Overall, these features of SHP654 gene therapy suggest that it may be a potential future therapy for hemophilia A.

The company will also present the recent developments of its new FIX gene therapy for the treatment of hemophilia B, with the study “SHP648: A high performing next generation FIX gene therapy vector based on AAV8.”

Researchers showed that the new SHP648 delivery method, based on a more efficient and potentially less toxic vector delivery system, was able to improve the levels of FIX by five times in mice. This beneficial effect was also associated with reduced response of the immune system, which suggests it may have prolonged positive effects.

These methods still require further validation and clinical development.

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