Long-Term Hemophilia A Therapies and Their Impact


Lisa Schrade, PharmD, and Robert Sidonio Jr, MD, MSc, discuss real-world evidence for hemophilia A therapies, highlighting their safety, efficacy, and impact on bleeding events, nurse visits, and hospital visits.

Jonathan Ogurchak, PharmD, CSP: Now with the product being out commercially available for the last couple of years, we’re starting to see some more long-term data surrounding how this is working in patients out in the wild, [as opposed to a] clinical trial–type setting. Dr Sidone, what have you seen in real practice [and] in real-world evidence as far as bleeds, nurse visits, hospital visits, etc?

Robert Sidonio Jr, MD, MSc: Obviously the clinical trial setting is important because that’s what gets you the approval for the drug, it dictates what the dosing is going to be. But when you participate in trials, you sort of understand how they’re figured out and why they choose certain dosing regimens. This is where the art of medicine is important, and it’s really important when you see a phase 3 trial that you look for those real-world studies, [those] phase 4 trials, because you want to see what happens in real life. You may have eliminated a lot of patients who participate in a trial because maybe they aren’t adherent, maybe they live far away, there could be a number of reasons. Oftentimes it isn’t always reflective of what your general population is. When you see it perform well in real-world studies, you get excited to say, “OK, well, this is definitely great.” And there have been a number of these. There have been some specialty pharmacy studies, there have been some long-term surveillance studies in other countries. More recently, they had a specialty pharmacy study, where it was a retrospective study, and they looked at electronic medical records and then pharmacy claims and tried to look at what the impact had been. These patients had to be on it for at least 6 months, because you want to see an impact period. What do you expect to see? There were fewer bleeding events, less factor usage, there were fewer nursing visits. The only thing they didn’t see a real difference was in emergency [department] visits. Those in the last couple of years are relatively a small number. It’s really hard to show a difference when it’s already small at baseline. Maybe over time you would see a difference. But like Dr Chowdhry has mentioned before, one of the concerns that we have is that there are so few bleeds that families have lost the art of how to do peripheral injections. You may see more visits to the emergency [department] than before. It may take some families some reeducation every once in a while. That’s where family camps and the summer camps where the kids learn how to stick themselves [come in]. If they ask me how to stick, it’s been a while since I’ve done it. Of course, it’s going to be difficult. My nurses are going to be significantly better at it. It just takes practice like anything else. It’s one of those life skills that I think patients need to retain, even if they haven’t done it on themselves. It’s good practice in some other settings.

But in real-world settings, the annualized bleed rate may be slightly higher than a trial. But remember, anytime you gave a dose in a trial, you have to have a really good reason. You couldn’t do it as prophylactic if they were going to do something that weekend. When we get phone calls and a kid has some injury, the safest thing to do is to give a factor dose. On a trial, you may observe that because you don’t know if it was an actual bleed. Families certainly haven’t been a much higher number, just a slightly higher number, as expected. You see this with factor products as well.

Jonathan Ogurchak, PharmD, CSP: There have been some other therapies that have been recently approved for hemophilia A as well that have shown some promise with safety and efficacy. So Dr Schrade, you’ve been talking a little bit more about how that might look.

Lisa Schrade, PharmD: The most recent product that just came onto the market was efanesoctocog alfa with the trade name Altuviiio. That one in their trials showed that it was well tolerated and inhibitors to factor VIII were not detected at all. That’s promising as far as its effectiveness. It does show that it does have a more prolonged half-life compared to other factor VIII products on the market, about 4-fold. And as far as annual bleed rate, they saw a 77% reduction in the patients who participated in the study after 52 weeks. It’s very promising and the nice thing about this factor VIII product, which is an infused product, [is it’s a] once-weekly dosing. We’ve even shifted above and beyond the extended half-life products that you had to dose twice a week, maybe 3 times a week, 10 out just once a week infusions at a set 50 units per kg of body weight.

Robert Sidonio Jr, MD, MSc: It’s really exciting. Again, it goes back to the option because initially people would say we have a [subcutaneous] product, why would you ever choose an intravenous [IV] product? Well, I mean this community understands intravenous injections. Most people in the family know how to do it. Certainly the mothers, girlfriends, wives, they all know how to do this, the aunts, everybody. What was really interesting is when you get emicizumab, you’re not achieving factor VIII; it’s a memetic, as Dr Schrade mentioned…, but you get an equivalence around 15% to 20%. You get this steady level, the half-life is 28 days, and so if you miss a dose here and there, it’s not going to change much. Obviously that’s great because you’ve maintained patience into basically a mild hemophilia phenotype. What’s interesting about Altuviiio…is that when you give an infusion, your levels go immediately to 100% or higher. In the majority of the week, you’re actually in what’s considered near normal or normal range, and particularly in adults, the majority of the week, they’re in the normal range. You can’t really achieve that with emicizumab. A lot of us wonder if this generation of thrombin, which is the ultimate goal and when you’re giving factor products, if you’ve normalized this, it probably has some long-term effects outside of that immediate period. You can imagine if you give this, this should be very protective of any kind of sports activities. We certainly know that you’re on factor prophylaxis or emicizumab prophylaxis. For the most part, you don’t have to alter anything, and you can participate in noncontact sports. But it does make you wonder about this product. You’re getting higher levels. And then the level that you’re going to is typically at or above where emicizumab would be the entire week. Then you give another injection. You’re really spending a long period of time in the normal range, which is pretty exciting. We’ve told our families that have switched to it, you can give it at night. It’s not a big deal. You don’t have to give it in the morning. Typically, [with] the factor products, you want to get the most benefit. As soon as you walk out the door, it’s nice to have good levels. But since it’s got such a…big area under the curve, you could give it, for example, Sunday afternoon. And you’re protected very well up until Wednesday, Thursday of that week. It’s a good option, another option for families. It just got approved not too long ago. We’ll have to see what the uptake is, but it’s great for the families to have another option for hemophilia.

Transcript is AI generated and reviewed by a Pharmacy Times editor.

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