The Implications of the Final Data From Hemgenix’s HOPE-B Trial

This is the second part of an interview with Steven W. Pipe, MD. For the first part, click here.

CSL Behring/uniQure’s etranacogene dezaparvovec (marketed as Hemgenix) is an FDA-approved adeno-associated virus (AAV) vector-based gene therapy intended to treat hemophilia B. It's approval was partially informed by primary analysis data from the pivotal phase 3 HOPE-B clinical trial (NCT03569891).

Notably, end-of-study results from HOPE-B were recently presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 6 to 9, 2025, in Orlando, Florida, by principal investigator Steven W. Pipe, MD, a professor of pediatric hematology/oncology at the University of Michigan Health. CGTLive® interviewed Pipe at the conference about the key data he presented and their implications. Pipe also discussed unanswered questions that remain with regard to these results.

CGTLive: How would you summarize the big picture implications of the new HOPE-B data presented at ASH this year?

Steven W. Pipe, MD: I think for patients who are interested in a genetic therapy like this, who want to be liberated from prophylaxis, this is really the only approach that really delivers that. It truly is a one-time infusion that can lead to a transformative impact for patients, liberating them from prophylaxis expression at a level which will provide effective bleed control.

I think now, with 5 years of follow up from this study, and then what we've learned from some other AAV trials in hemophilia B, it's really giving a good confidence about the long term safety for this therapy. What we also heard at this meeting is that for the Hemgenix commercial product that became available after the primary analysis, we just hit a milestone: 50 patients in the United States have now received this commercially, in addition to the patients who participated in the clinical trial. This is growing on a global basis as well, and so the follow-up for those patients over time will also give us continued insights on efficacy as well as safety over the long-term.

Are there any remaining unanswered questions with regard to this data or areas of interest for more study?

I think some of the open questions are around whether we could prevent the transaminitis reaction—even though it's in a minority of the patients, I think there's still some questions about whether there are some immunosuppression protocols which could be applied, which could eliminate that reaction and maybe salvage higher expression in those individuals. That will require some additional studies to really determine whether we should be using alternative immunosuppressants or maybe moving to a prophylactic approach. But for now, corticosteroids do seem to be salvaging the factor IX expression and still allowing patients to have durable efficacy from this treatment.

Is there anything else you want to add about this?

I was also excited that the the end-of-study publication is now available at the New England Journal of Medicine as of yesterday when we gave the presentation. It provides some additional great charts and graphs in there that add to what I was able to present at this meeting.

This transcript has been edited for clarity.

For more coverage of ASH 2025, click here.

REFERENCES
1. Pipe S, Miesbach W, Recht M, et al. End-of-study analysis of the HOPE-B trial confirms the durable efficacy and safety of etranacogene dezaparvovec hemophilia b gene therapy over 5 years. Presented at: ASH 2025 Annual Meeting. December 6-9, 2025; Orlando, FL. Abstract #538