Optimizing Emicizumab Therapy in Hemophilia Treatment


Regarding optimal use of emicizumab for patients with hemophilia, the expert panelists dig into the details of safety, efficacy, dosing, and administration for this agent.


Peter L. Salgo, MD: A couple of things come to mind. First of all, it’s very important—this is almost lost in the noise, and I don’t want this to get lost—it’s [emicizumab’s] not intravenous (IV)?

Robert F. Sidonio Jr, MD: It’s not IV. It’s a subcutaneous route.

Peter L. Salgo, MD: How many cc’s?

Tim Boonstra, RPh: Typically, you can infuse 1 to 2 mL at a time. Obviously as you get older, you might have to do 2 injections, or if you’re doing once-a-month injections.

Robert F. Sidonio Jr, MD: Or if you are a higher weight.

Tim Boonstra, RPh: Yes, if you’re a higher weight, you might have to do it since it’s a weight-based dose.

Peter L. Salgo, MD: Two injections once a month as opposed to a bunch of cc’s every couple of days?

Robert F. Sidonio Jr, MD: And regarding the volume for an inhibitor patient, if APCC [activated prothrombin complex concentrate] volume could be 100 or 120 mL, you’re talking about comparing that with 5 or 6 mL. It’s just dramatic.

Peter L. Salgo, MD: That’s big. And again, it’s once a month.

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: Does it maintain effectiveness continuously across those months?

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: Or is the effectiveness such that because it increases, you’ve reached the end?

Robert F. Sidonio Jr, MD: There’s a specific loading regimen in which you have to load at a specific dose of 3 mg/kg weekly. Once you reach that steady state, there are very few peaks and trials because the half-life is 28 days. They didn’t compare them directly, the every-2-weeks injections and every-4-weeks injections, but it provides that option. The great thing is, you’re not dosing more. If you give somebody it once a month, you’re giving them the same monthly amount as somebody getting it once a week, which I think is a good option for the pharmacist as well. We’re not encouraging people to use more product; they just get a choice in what works best for them. We don’t know if once-a-week is better protection than every 2 weeks, but maybe for the active children once-a-week might be better. Sometimes you worry about people forgetting to do it. If you do it once a month and you miss a week or 2, you might start to drift down a dose.

Peter L. Salgo, MD: I was going to ask about that.

Tim Boonstra, RPh: That is the challenge. We have a lot of patients who are not adherent to their regular, standard half-life or extended half-life prophy regimen, and most likely, if they’re not adherent to that, they won’t be adherent to this.

Peter L. Salgo, MD: But let’s not blame the patients completely.

Tim Boonstra, RPh: Yes.

Peter L. Salgo, MD: There’s the famous study, right, in which they gave medical students—highly motivated, one would think intelligent—and they gave them placebos. All they asked them to do was to take 1 pill a day for a year. And then, they looked at the number left over, and it was about 30%. This is not bad, people.

Robert F. Sidonio Jr, MD: This is a human problem.

Peter L. Salgo, MD: This is a human problem, right.

Robert F. Sidonio Jr, MD: I forget to take my Zantac [ranitidine] every day, I can tell you. I just forget to take it. I notice it later and then I take it again.

Tim Boonstra, RPh: I think that for some of those challenging patients, if we have the options to go once a week, every other week, or once a month, we can have them come into clinic and give them their shot. At least we know that they’re adherent.

Robert F. Sidonio Jr, MD: We hope that you are going to help provide reminders. We always tell people that you have phones, to set reminders, but not everybody does that. We’re still going to rely on the pharmacist to keep track, and these medical bleeding logs are going to be important.

Peter L. Salgo, MD: Why do I always come to, “There’s an app for that?”

Robert F. Sidonio Jr, MD: Yes.

Peter L. Salgo, MD: Once a month, your phone goes off. That should work.

Robert F. Sidonio Jr, MD: And as he mentioned before, one of the apps does have a way to connect to your pharmacist and connect to your center, so I can track it and see he forgot to give his dose last week. And then, one of us will make a call.

Peter L. Salgo, MD: There’s a black-box warning. We can’t go past this without discussion on emicizumab. What is this black box? It sounds scary. Is it scary. Should it be scary?

Robert F. Sidonio Jr, MD: I was involved in the clinical trials. What happened was in the first trial, the HAVEN 1 study, when patients bled, you still had to use those bypassing agents that we talked about, APCCs or recombinant factor VII. What we learned is that now that you’re on emicizumab, you don’t need to use doses as high. Unfortunately, during first bleeding somebody used a very high dose of APCCs, and they developed a sinus thrombosis. And then, there were a few other events that developed, and they developed something called thrombotic microangiopathy.

Peter L. Salgo, MD: Sounds scary.

Robert F. Sidonio Jr, MD: Thrombocytopenia, acute renal injury, and microangiopathic hemolytic anemia. What we learned was the unifying characteristic is that they were getting over 100 units/kg in a 24-hour period of that APCC. And so, a “Dear investigator” letter came out. We were all warned to look for this, not to do this. And since then, we have not seen any of those events because we’ve shifted the use to recombinant factor VII.

Peter L. Salgo, MD: It’s interesting to me that the problem was not insufficient clotting…

Robert F. Sidonio Jr, MD: No.

Peter L. Salgo, MD: But overaggressive clotting if you take that, because you could pull back on that.

Robert F. Sidonio Jr, MD: It is different. As you know, and we tell these patients, if we have a kid who trips and hits their head, we’re throwing the kitchen sink at them because we know they could be treating that bleed for a month afterward. We often say to be aggressive; give factor first, ask questions later. It’s the same when they show up in the emergency department [ED]. We tell the ED doctor, “If the mom says he hit his head, give the factor and then scan his head.” And so, our mentality has changed in that if that guy fell and hit his head, we probably should observe him, look at it, then decide whether we want to give it.

Peter L. Salgo, MD: If he’s on emicizumab.

Robert F. Sidonio Jr, MD: If he’s on emicizumab. It’s a slightly different mentality that we all have to get used to.

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