What Is It Like To Receive Gene Therapy?

David Page 05:21
Who was involved in that process, in your own personal process before the final decision? I guess your treating physician? And what about your family?

Brian O’Mahony 05:29
My treating physician, the research nurse, some of my colleagues and friends abroad who are clinicians who had various views around gene therapy, some people with hemophilia, like yourself, David, with whom I discussed this. With my family, to some extent, but not an enormous extent. My wife and kids tend to trust my judgment on this. And I explained it to them, but we didn't have long, detailed discussions on this because they know that I'm very familiar with the therapeutic landscape. And they fully supported my decision on this.

David Page 05:57
What are some of the things people absolutely need to understand before embarking on this journey?

Brian O’Mahony 06:03
You need to set and manage your expectations. You don't know how long it will last. You don't know what factor expression you will get. You don't know if you're going to get any increase in factor expression. You don't know if you need to take steroids. And there's obviously some theoretical concerns around long-term safety. So you need to be prepared for a range of outcomes there. So, if you go in thinking, “I want at least 15 years, I want a factor level of at least 50%, and I don't want to take steroids, ” if you don't get that outcome, that it's a failure, then you're not ready for gene therapy, You need to be aware, “Okay, I'd like this factor expression. But I'm aware I could get this range. I'd like this durability, but I can’t predict that,” and be ready for steroids. So, for example, with steroids, for factor VIII gene therapy, about 80% of the people on the trial had to take steroids for an average of seven months. So, if you're going to take factor VIII gene therapy, I think you work on the assumption that you're going to have to take steroids. With the factor IX gene therapy that is licensed, it was under 20% needed steroids for a shorter period of time. So you could probably think I may have to take steroids but it's less likely, but you just need to be aware of the range of expressions that you get. That's really important. So if you're hoping for 50% and you get 5%, you're going to be disappointed, but you need to be able to say, ”Okay, well, I knew this was a possibility. And I'm okay with that.”

David Page 07:22
So you're trying to avoid buyer's remorse? I've heard you use that expression before.

Brian O’Mahony 07:27
Absolutely. Treatment remorse. You don't want to go back to the clinician ... I don't want any of our members coming back to us in a couple of years’ time saying, “I wish you hadn't persuaded me to take gene therapy.” We're not going to persuade anybody. We're not going to persuade or dissuade. We're going to try and make sure that everybody who's considering gene therapy takes a fully informed decision for themselves.

David Page 07:45
People might imagine that the administration of gene therapy is an elaborate process. Can you describe that day?

Brian O’Mahony 07:52
It's actually not an elaborate process. I was asked one question at a meeting abroad about how long I had to stay in hospital. And did they have to replace all my white cells? it took three hours. It's a simple infusion. It's like getting a bag of plasma. You go in. Obviously, they take some bloods. At the last minute, they check to make sure you want to go ahead with this. And then you get the infusion. The infusion itself took about 80 minutes. It's about a liter of liquid, a very easy process. So I was
quite relaxed. It was a very easy process. But having said that, when I looked around me, you're got the clinician, you're got the resource nurses. Outside, you had the clinic director, you had the research director, you had a crash team ready to go, So there were a lot of people looking on because it's the first gene therapy that was actually done in the hospital. A very easy process but I must say, when I went home that night, I was emotionally exhausted because I was aware, this was a fairly momentous day.

David Page 08:46
We've heard from guests in this podcast series about the importance of very close follow-up in the weeks and months following gene therapy. What was that like in your case?

Brian O’Mahony 08:56
In the first year after gene therapy, I had to make 30 visits to the hospital. Now you have to actually go in once a week for the first three months, I actually exceeded that. I went in twice a week to have an extra liver blood test done. So I certainly didn't want to take any chance of missing an increase in liver enzymes. And I didn't think once a week was often enough. So I did this. I was fully aware of this. And so I was committed to it. I'd set aside the time. And, in fact, because it was during the COVID pandemic, there was more of a concern about going to a hospital at that point in time, but they managed it very well in the non-clinical setting.

David Page

Why is this frequent follow-up so important?

Brian O’Mahony

Well, first of all, you need to know what your factor expression level is and how that's changing, and that can change. With the liver enzymes, you want to monitor liver enzymes very carefully. You can't take the chance of missing an increase in liver enzymes even for a couple of days because that could lead to a loss of expression of the factor and you can't get that back. You need to look at your ultrasound scans for your liver health, joint scores and also to add knowledge about outcomes. And so it really is very, very important. But certainly the factor expression level and the liver enzymes are both tests, by the way, which can be done in a local hospital.