Dosage and Administration of Anti-CGRP Monoclonal Antibodies for Migraine

Stephen Silberstein, MD: I think what we should do is, each of you take a drug and tell us how it can be given. Erenumab.

Andrew Blumenfeld, MD: Erenumab, I like to use at the 140 mg dose rather than the 70 mg dose. Across all the different endpoints that were done in the trials, there is a preference for the 140 mg compared to the 70 mg. I certainly agree with you that you need to do this long term. The chronic migraine trial, the Pivotal Phase II, was only a 3-month trial. In clinical practice, it certainly needs to be used for much longer than that, and I favor the 6-month trial period.

Stephen Silberstein, MD: Seventy mg and 140 mg cost the same, is that not correct?

Andrew Blumenfeld, MD: The price is the same.

Stephen Silberstein, MD: Yes. That’s important.

Andrew Blumenfeld, MD: We now have a 140-mg autoinjector, which has just been released, so we no longer have to do the 2 injections of the 70 mg.

Stephen Silberstein, MD: Fremanezumab.

Deborah Friedman, MD, MPH: Fremanezumab comes in 225-mg prefilled syringes. At this point, it does not come in an autoinjector, but they’re working on that. It’s given subcutaneously, either 225 mg a month, or 3 doses, 675 mg, every 3 months. A lot of people are starting their patients on monthly dosing. Most patients also prefer to start with monthly dosing. It’s a little intimidating to think about having something in your system for 3 months, and you don’t know what’s going to happen with it. Then, we transition those patients who prefer quarterly dosing using the 3 injections at once.

Stephen Silberstein, MD: I tend to give everybody quarterly dosing because if you look the benefit of only having it every 3 months, and the fact that, by suddenly giving a boost, you reach steady state levels quicker, theoretically there’s a chance they will improve faster.

Deborah Friedman, MD, MPH: They actually did a study of patients who were in the open-label extension and asked them if they’d prefer quarterly dosing or monthly dosing. People overwhelmingly wanted quarterly dosing, but I think you have to keep in mind that the people in the study were getting dosed every month with 3 injections in order to maintain the blinding.

Stephen Silberstein, MD: I’m not disagreeing about the blinding.

Deborah Friedman, MD, MPH: So under those circumstances, I think I would have preferred quarterly dosing, as well.

Stewart J. Tepper, MD: There is a comforting aspect of fremanezumab that was presented at this meeting. There was a pretty systematic analysis of whether there was any wearing off of the quarterly dosing, and there appeared not to be.

Deborah Friedman, MD, MPH: There does not appear to be.

Stewart J. Tepper, MD: Yes, it was very encouraging.

Stephen Silberstein, MD: That’s the important point. The other advantage is, if you have samples in your office, and you give them 3 injections, you’ve got 3 months to get pre-approval. If you give them 1 injection, it may not get approval before the next dose is there.

Deborah Friedman, MD, MPH: I’ve done it.

Stephen Silberstein, MD: From a practical point of view, that’s what I do.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: It’s also reassuring to know that in very early studies, it was even given at 900 mg monthly and established as pretty safe. That’s something you can also tell patients who may have any hesitation about taking 3 shots at once.

Stewart J. Tepper, MD: One last point about fremanezumab that it’s worth pointing out in terms of the early chronic migraine studies, is that they actually studied patients like those we see. They studied patients who had continuous headache. They studied patients who had had multiple preventive medicine failures and were on prevention at the time, and it worked equally well as in less severe patients in the phase 3 trials. They actually have good evidence on fremanezumab.

Stephen Silberstein, MD: There’s a study that’s going to be published looking at recruiting patients who failed multiple drugs with fremanezumab, and that data should be presented soon.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: So galcanezumab would be me?

Stephen Silberstein, MD: Yes.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: That one is the simplest, because there’s really only 1 way to give it. What’s unique is that it was studied and is administered with a loading dose up front, so 240 mg for the first dose, then 120 mg monthly thereafter. There are no decisions to be made, once you pick that drug, about how to dose it. You just do it 1 way. Having a loading dose means that you achieve steady state at 1 month as opposed to 5 to 6 months, or 5 half-lives. That may or may not translate to sooner establishment of efficacy and longer duration of benefit. We don’t really know, but at least it keeps things simple, and it is in an autoinjector, a pretty easy-to-use one, as well.

Stephen Silberstein, MD: It’s the same for Trulicity.

Deborah Friedman, MD, MPH: They have a syringe now, too.

Stephanie J. Nahas, MD, MSEd, FAHS, FAAN: Yes.

Stewart J. Tepper, MD: One other point about galcanezumab that’s exciting and was presented at this meeting, is that 300 mg for galcanezumab—not the dose that we’re talking, which was 240 mg load and 120 mg monthly—was effective in preventing episodic cluster headache and has been submitted to the FDA for that indication. The FDA agreed to an expedited review, and I would assume that galcanezumab as a preventive medicine for episodic cluster headache will be approved this year.

Stephen Silberstein, MD: We talked about the injectable formulations. I think it’s important we talk about the other one in development that’s given intravenously. Can you tell us a little bit about that?

Stewart J. Tepper, MD: The fourth is eptinezumab, and it has been submitted to the FDA for prevention of migraine, as Deb pointed out, both episodic and chronic. Eptinezumab, assuming that the FDA approves what was submitted, will be available as a 100-mg or 300-mg infusion that we would administer in an infusion suite quarterly for patients. It has an interesting feature, which is that it very clearly shows benefit within the first 24 hours after infusion, which would make sense. We know from gepants that if you block the CGRP [calcitonin gene-related peptide] receptor acutely, you can terminate a migraine. In this case, you’re taking out all the CGRP virtually instantly with an infusion, and within the first 24 hours, there’s a 50% drop in the likelihood of a migraine.

Stephen Silberstein, MD: I think the important point is the fact it is not the antibody that’s different, but the route of administration is different.