First results from gene therapy trial in haemophilia B

The phase 3 HOPE-B gene therapy study in patients with severe or moderately severe haemophilia B met its co-primary endpoint. Following a single dose of etranacogene dezaparvovec, factor IX activity increased to near-normal levels after 26 weeks. These first results from the largest gene therapy trial cohort to date support a favourable safety and efficacy profile of etranacogene dezaparvovec [1].

Treatments for haemophilia B or factor IX deficiency are limited to regular intravenous infusions of factor IX concentrates. The goal of gene therapy in haemophilia B is a single procedure that establishes long-term benefit with sustained factor IX activity, providing effective protection against spontaneous bleeding, eliminating the need for continuous prophylaxis, and improving quality of life.

Etranacogene dezaparvovec (AAV5-Padua hFIX variant; AMT-061) is an investigational gene therapy for haemophilia B. It combines an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimised Padua variant human factor IX gene with a liver-specific promoter.

Prof. Steven Pipe (University of Michigan, USA) presented the 26-week outcomes of the phase 3 HOPE-B trial (NCT03569891). Of 67 haemophilia B patients enrolled in a prospective lead-in period, 54 participants (44 with severe and 10 with moderately severe haemophilia B) were dosed and completed the 26 weeks of follow-up. Mean age was 41.5 years. Importantly, this study included patients with pre-existing anti-AAV5 neutralising antibodies; 42.6% had neutralising antibodies at baseline. During the lead-in, 70.4% had bleeds despite prophylaxis.

Following treatment, factor IX activity increased rapidly to a mean of 37.2% at week 26, representing a mean change from baseline of 36.0% (P<0.0001). In the first 26 weeks after treatment, 72.2% of patients reported no bleeds. Patients were able to discontinue prophylaxis and bleeding was abolished in most patients throughout the 26 weeks. Overall, 68.5% of patients had a treatment-related adverse event post-treatment, the majority of which were mild (81.5%). Most common adverse events were transaminase elevations requiring steroid treatment and infusion-related reactions. This profile was consistent with early phase AAV5 studies.

The final analysis of the HOPE-B study is planned at 1 year to support marketing authorisation applications of etranacogene dezaparvovec.

1. Pipe SW, et al. First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract LBA-6.

Posted on 18 February 202117 May 2024