Integrating Gene Therapy into Clinical Care for Hemophilia B

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

At the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 6 to 9, 2025, in Orlando, Florida, end-of-study data were presented from the pivotal phase 3 HOPE-B clinical trial (NCT03569891) that supported the FDA’s 2022 approval of CSL Behring/uniQure’s etranacogene dezaparvovec (marketed as Hemgenix), which is an FDA-approved adeno-associated virus (AAV) vector-based gene therapy intended to treat hemophilia B. At the conference CGTLive® interviewed HOPE-B principal investigator Steven W. Pipe, MD, a professor of pediatric hematology/oncology at the University of Michigan Health.

After asking Pipe about the findings and their implications, CGTLive asked Pipe more generally about what clinicians thinking about incorporating the commercial product into their practice need to know. Pipe went over key considerations for infrastructure, speaking to patients about the treatment decision, and more.

CGTLive: What infrastructure does a practice need to start delivering gene therapy?

Steven W. Pipe, MD: Well, with an effective therapy like Hemgenix has been showing to be, the question then is, how do we translate this into clinical delivery at our hemophilia treatment centers? This has actually not been without some challenges. Doing this in the clinical trial setting, with all the supports and infrastructure there, is quite different from most centers when we're talking about integrating this into clinical delivery. Even at my center, we've had to think about what sort of infrastructure we need to develop, what kind of education we need to provide for our multidisciplinary staff, what additional staff might we need in order to be able to deliver this effectively—and that's actually been a process over a couple of years to get to the point where we can now actually start to offer this to patients.

How do you speak to the patients and their families about whether gene therapy might be a good choice for them?

I think this end-of-study report really gives us great data to share with patients because we can talk about the efficacy and we can talk about what we know about the safety. Even though we still have a wide range of expression levels of factor IX, the fact that the vast majority of individuals are going to be in the normal-to-mild hemophilia range is something that we can share with patients and avoid complications of having super-physiologic levels. Really [it’s] a very minority of patients who are not going to be at a level of expression that's going to give good efficacy.

Then on the safety front, we're comparing that against remaining on standard-of-care therapy, where we already know what the outcomes are, particularly as it relates to progression of joint disease over decades. What I'm excited about sharing with patients is the earlier you could have a transformative therapy like this, the better for bleed protection over the long-term.

Right now, it's only offered to adults, but I think for young men, who are of age (18 or older), this is something we want to incorporate into our shared decision-making about their therapy, and I think we have great data to be able to encourage them in that regard.

There is an active study, actually, that just launched this year where we're now going to be offering this to the adolescent population. And so that study will read out over the next couple of years, but I'm excited for the first time be able to offer this to an even a younger cohort of patients with hemophilia B.

After the patient receives the initial treatment, what does the long-term follow-up look like?

The rigors of a investigational trial are usually much greater than is needed for a clinical delivery, but we do have to watch carefully after the initial dosing for the transaminase elevations and then be ready to respond with a course of corticosteroids. That usually involves at least weekly or maybe even twice weekly lab draws. But we've been able to leverage doing this through local labs, and so we've been able to reduce the commitment of the patients to be coming back and forth to the clinic. We can have them go to a local laboratory, and we can work with them at arm's length for that monitoring. I think it's made this a much more manageable experience to do this in partnership with the patients, using their local resources, and just reduces the burden of having to come back to the to the university center often. And really, we've not seen any unique challenges in the community setting of the follow-up so I think, again, when we're talking to patients about this, we we can work around their work schedules, and this doesn't have to be a majorly disruptive process. Once you get past the first 12 to 20 weeks or so, the follow up is much less. And certainly, being liberated from prophylaxis is just a great thing for these patients to free them up.

Has the integration of gene therapy changed the way you work with specialists from other fields?

I think we are seeing in some campuses the infrastructure to support genetic and cellular therapies is coming collaboratively under an umbrella, so we have an opportunity to work with our colleagues in neurology, ophthalmology, and other rare genetic diseases, and take advantage of some collective infrastructure and experience.

However, I still think for the actual delivery of the therapy, this is still going to be solidly within the clinical experience, because for a patient who wants to make this choice, I think they want to make it with their physician who’s been looking after them over the course of their life. And so I think this is still going to be part of the intimacy of our hemophilia treatment centers in actually delivering this transformative therapy.

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