Brian O Mahony FACSLM
Chief Executive, Irish Haemophilia Society
Haemophilia is an inherited bleeding disorder caused by deficiency in one of the clotting factors – either FVIII or FIX. Research is currently underway to assess the use of gene therapy to help treat the disorder.
Current licensed therapies for haemophilia involve regular intravenous injections of the missing clotting factor to prevent or treat bleeding episodes. A subcutaneous clotting factor mimetic is also available now in Ireland as a treatment for Haemophilia A.
Haemophilia is an ideal disease for treatment with gene therapy as it is a single gene disorder, requiring the replacement of only one clotting factor and normal levels of factor are not needed to significantly improve health related quality of life. The missing clotting factor protein can be provided by delivering the gene in a suitable carrier (usually an adeno associated viral vector) to the liver as a “one-off” infusion.
Future research into haemophilia
There are currently more than 30 clinical trials underway in haemophilia gene therapy with several in advanced phase 3 trials. The most recent published results in a FVIII phase 3 trial in 134 men reported data one year post infusion of the vector. They reported a mean FVIII expression of 43.6% with a median of 24.2%. Eighty per cent of participants had no bleeding episodes from five weeks post vector dosing to the end of year one.
There are currently more than 30 clinical trials underway in haemophilia gene therapy with several in advanced phase 3 trials.
Data was recently reported also on a phase 3 FIX clinical trial using a modified enhanced FIX gene. Six months post vector infusion, the 54 participants had a mean FIX expression of 37%. This trial includes three Irish participants all of whom have achieved very good factor expression to date.
There remain unanswered questions in relation to predictability of factor expression, duration of response, the proportion who will not respond and long-term safety. The economics of gene therapy will also require new and imaginative thinking in relation to payment models, perhaps with a pay for performance type model being considered. We have travelled from the theoretical to the point where now we have people with haemophilia in Ireland already treated with gene therapy as part of a clinical trial. The work progresses and the future awaits.