Hope for Uniqure, at the third time of asking

Uniqure’s persistence with the Hope-B study has been rewarded with a dataset that looks to back the approvability of etranacogene dezaparvovec as the first haemophilia B gene therapy. The study had been delayed and modified twice, and suffered a brief US clinical hold. The FDA apparently needed reassurance that entranadez’s effect was not transient: Hope-B’s primary endpoint was changed from six-month factor IX levels, to co-primaries including one-year FIX levels and one-year annualised bleeding rate (ABR), and then to a sole primary of 18-month ABR, specifically 52 weeks after achievement of stable six-month FIX levels. Today the group and its partner CSL Behring said entranadez had met this metric, with ABR of 1.51 at 18 months versus 4.19 in the six-month lead-in in the 53 evaluable subjects, a result that backed non-inferiority as well as superiority to baseline FIX prophylaxis. The durability question appears settled, with mean FIX activity of 36.9% of normal at 18 months versus 39.0% at six, the slight fly in the ointment being that 12-month FIX activity was numerically higher still, at 41.5%. Changes to Hope-B had delayed entranadez filings to 2022; Uniqure today confirmed that this was now on the cards.