Appropriate Selection of Emicizumab for Hemophilia


Expert panelists establish the appropriate settings in which to switch over to or start patients on emicizumab, given the available clinical data and understandings of patient preference.


Peter L. Salgo, MD: Now we have 2 classes of patients: those with blockers and those without. We have 1 agent, a new agent, that can reduce the rate of bleeding in both groups. Who do you switch over?

Robert F. Sidonio Jr, MD: I think for the inhibitor patients, it’s a straightforward discussion. Obviously, there’s a debate about when you should get rid of an inhibitor. I said this before, we’re looking at whether you can use Hemlibra [emicizumab] with our current ITI [immune tolerance induction] regimens. But it gives patients an option, that’s what’s great. If they don’t feel like they can do the immune tolerance regimen, or if it’s just not possible for them in their life at that time, then this is a great alternative to reduce their chance of bleeding. It’s going to be more challenging in the noninhibitor patients because, as you know, there are plenty of patients who are doing extremely well on factor replacement. They have learned to deal with this and it’s as that old saying goes, “If it ain’t broke, don’t fix it.” Some of those patients certainly will not switch. They may not use that phrase in New York, but they use it down in Georgia.

Peter L. Salgo, MD: Oh, they use it in New York.

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: But the treatment that you’re not changing is intrusive.

Robert F. Sidonio Jr, MD: Sure.

Peter L. Salgo, MD: They’re used to it, right? But it’s still IV [intravenous therapy] every few days. This is a lot.

Robert F. Sidonio Jr, MD: Yes. Once a week or once every 2 week subcutaneous injection. But I think it’s great that the families have an option. We inform them and say there’s more data. Obviously, with factor VIII, we have data on that from decades of use. Some families feel comfortable. You have to think about it. If their grandfather was on factor or their brother is on factor, they might feel connected to that community. It becomes more complicated than saying this therapy is better than the other.

Tim Boonstra, RPh: Yes, and when they put somebody on emicizumab they may think that they’re “cured.”

Robert F. Sidonio Jr, MD: Yes, invincible.

Tim Boonstra, RPh: But how do you work with a patient who now wants to be more physically active? To what degree do you provide bleeding doses? It brings up a few other challenges.

Robert F. Sidonio Jr, MD: There are a few unknowns in there. That’s the only reason some people might tread lightly.

Peter L. Salgo, MD: You’re not going to advise somebody on emicizumab to go play in the NFL [National Football League].

Robert F. Sidonio Jr, MD: No, definitely not.

Peter L. Salgo, MD: Not even as a punter.

Robert F. Sidonio Jr, MD: We advise most of our children not to play football in general, so yes. Again, we don’t want them to say, “Oh, I can do all those sports I never could do.” We have a little less information about sports. But I can tell you that on the trial, we had kids who had inhibitors that had never been to a park before, which I thought was just devastating as children. Can you imagine? They just couldn’t deal with restricting them at a park. And then they were feeling better, and they just let their kids run loose. I saw a kid last week who’s finishing up on the trial, and he has 6 siblings and they play flag football with each other. His mom says that before, he would bleed and he’d have to sit and watch; now he’s participating and he feels great about it and he doesn’t think anything of it. Obviously, he felt good enough to participate now.

Peter L. Salgo, MD: We talked about HAVEN 1 and HAVEN 2 [clinical trials]. You alluded to HAVEN 3.

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: Is that the trial you’re talking about now?

Robert F. Sidonio Jr, MD: Yes. That’s the trial in which they looked at the ability to work in noninhibitor patients.

Peter L. Salgo, MD: We had patients clearly with inhibitors, so now let’s try it in the rest.

Robert F. Sidonio Jr, MD: Yes, let’s try it. We feel like it works just as well in non-inhibitor patients and they demonstrated that there was a tremendous benefit for that. We had teenagers involved in that study, and obviously a lot of adults as well. They switched over from their factor VIII concentrate to this product and there was a dramatic reduction in bleeding events. It was an 80% to 90% reduction rate. You don’t see many clinical trials where you see that kind of dramatic reduction. Again, they tested patients who were on factor VIII prophylaxis. We measured some of them for a period of time and then they went on the study and we measured them the same way, and they had a significant reduction in their bleeding, even with that. It was a very good design to answer the questions you wanted answered.

Peter L. Salgo, MD: And this has been published?

Robert F. Sidonio Jr, MD: Yes, these have been published in various settings and presented as trials.

Peter L. Salgo, MD: I come back to this. Let’s put money aside, just for a moment. I know everyone’s got money issues. I understand people also trust factor VIII. They’ve had factor VIII in the family for a long time. But notice that I keep coming back to the commercials: “This ain’t your father’s Oldsmobile.”

Robert F. Sidonio Jr, MD: Exactly.

Peter L. Salgo, MD: We’ve moved on.

Robert F. Sidonio Jr, MD: It’s not your father’s hemophilia.

Peter L. Salgo, MD: It’s not my dad’s hemophilia anymore. Why wouldn’t you just start everybody on this new molecule where there’s almost no downside, other than that it costs money. But everything costs money.

Robert F. Sidonio Jr, MD: Yes.

Tim Boonstra, RPh: Lacey brought up a good point earlier about osteoporosis in hemophilia patients. If you totally eliminate the need for factor VIII, what does that do to someone’s body? And to be honest, we don’t know. For patients who start when they’re really young, especially a patient who doesn’t have an inhibitor, what does a lifetime of no factor VIII look like?

Peter L. Salgo, MD: Lacey, was the implication of your statement that factor VIII was contributing to the osteoporosis?

Lacey Chapman, RPh: No. It could be doing the opposite. It could be that factor VIII is helping the bones and preventing osteoporosis. That’s why the lack of factor VIII might lead to osteoporosis.

Robert F. Sidonio Jr, MD: We know that patients on blood thinners have the same issue. Is it because they don’t make enough clot? It might have nothing to do with the factor VIII at all, we don’t know that. Does this mimic all the other factor VIII functions? We’re all focused on the clotting stuff. Factor VIII does other things outside of the clotting cascade.

Peter L. Salgo, MD: Just when I thought it was safe to put down my textbook. What other things?

Robert F. Sidonio Jr, MD: Bone mineral density. We think it does play a role in that.

Peter L. Salgo, MD: Factor VIII.

Robert F. Sidonio Jr, MD: Factor VIII, and probably factor IX as well. We don’t know. Is it because the kids are not participating and doing exercise like their counterparts? Or is it something intrinsic such as the lack of factor VIII? We’re replacing it, but we’re not replacing it at the same rate. These are all things that we’re going to learn, and they’re a little bit more of a minor issue obviously than bleeding.

But take a baby who was just born and their family has no family history, or they have a family history and everybody in their family is on factor VIII. These conversations are about hour-long conversations because you’re explaining the whole history of hemophilia and what the current therapies are. There are still unknowns, right? If we put them on emicizumab, they’re still probably going to develop inhibitors to factor VIII because when they bleed, they have to get factor VIII. Does it matter? Maybe it doesn’t matter.

We might delay their inhibitor formation until they’re adults. Is that OK? There are just a lot of potential unknowns. I think these are all good things. It just tells us that we need to continue to do research in this area until we’re done. We don’t need to shut down the pharmacies and say, “Well, it’s simple now to just drug. We don’t need this.” We still need those experts to take care of patients.

Peter L. Salgo, MD: If you look at big things first, life and death, if you’ve got a drug here that will keep people alive with less risk, that’s a good drug.

Tim Boonstra, RPh: Absolutely.

Peter L. Salgo, MD: Now, we’ll worry about bone mineral density.

Robert F. Sidonio Jr, MD: Sure.

Peter L. Salgo, MD: We’re not going to know about that for maybe a generation.

Robert F. Sidonio Jr, MD: Sure.

Peter L. Salgo, MD: And giving them factor VIII is not necessarily a bad thing from that perspective, but it is a bad thing for lots of other reasons

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