CSL Behring files for MAA of haemophilia B gene therapy

Marburg-based CSL Behring has filed for accelerated EU marketing authorisation of Etranacogene dezaparvovec (EtranaDez), the first haemophilia B gene therapy. The application is based on the Phase III HOPE-B trial, which showed a durable and sustained therapeutic effect after a single infusion. Etranacogene dezaparvovec is an adeno-associated virus 5 (AAV5)-based gene therapy licensed from Uniqure NV  for use as a single treatment for haemophilia B patients with a severe bleeding phenotype.

In haemophilia B patients with severe bleeding phenotype treated with etranacogen decaparvovec, the adjusted annualised bleeding rate (ABR) was reduced by 64% and the drug was shown to be superior to prophylaxis treatment 18 months post-treatment compared to a 6-month run-in period. In addition, there was a stable and durable increase in mean factor IX activity (FIX). Etranacogene dezaparvovec is specifically designed to enable near-normal blood clotting ability by targeting the underlying cause of the disease: a faulty F9 gene that causes a deficiency in clotting factor IX (FIX). The AAV5 vector carries the Padua gene variant of factor IX (FIX-Padua), which produces FIX proteins that are 5x-8x more active than normal.

Preclinical and clinical data show that AAV5-based gene therapies can be clinically effective in up to 95 per cent of haemophilia B patients with pre-existing antibodies to AAV vectors. Results from the pivotal HOPE-B trial showed that etranacogen decaparvovec achieved a mean FIX activity of 39.0 IU/dL six months after infusion and 36.9 IU/dL 18 months later. After the six-month post-infusion phase-in period, the adjusted annualised bleeding rate (ABR) (1.51) was reduced by 64 per cent (p=0.0002) for all bleeds and by 77 per cent (3.65 to 0.83; p<0.0001) for all FIX-treated bleeds over months seven to 18. In addition, 98 per cent of subjects treated with a full dose of etranacogen decaparvovec discontinued prophylaxis, resulting in an overall 97 per cent reduction in mean unadjusted annualised FIX consumption from 257338.8 IU/year/participant to 8486.6 IU/year/participant (from the initiation phase to months 13-18).