Matt Hoffman, Senior Editor for NeurologyLive, has covered medical news for MJH Life Sciences, NeurologyLive’s parent company, since 2017. He hosts the NeurologyLive Mind Moments podcast, as well as Second Opinion on Medical World News. Follow him on Twitter @byMattHoffman or email him at firstname.lastname@example.org
The director of the Pediatric Headache Program at Children’s Hospital of Philadelphia spoke about the potential for CGRP inhibitors to find use in pediatric patients.
Christina Szperka, MD
In May, erenumab (Aimovig, Amgen/Novartis) was granted approval by the FDA for the treatment of migraine. It was a landmark moment. Erenumab became the first approval in a class of calcitonin gene-related peptide (CGRP) inhibitors, with several others already awaiting decision by the approving agency.
Migraine, a condition which has needed efficacious preventive therapies for years, finally got one—for adult patients. But the condition persists in pediatric patients, many of which have failed multiple acute treatment options, said Christina Szperka, MD.
Szperka, a pediatric neurologist and the director of the Pediatric Headache Program at Children’s Hospital of Philadelphia, spoke with NeurologyLive about the potential for CGRP inhibitors to find use in pediatric patients, and what steps have been made in the space in recent years.
Christina Szperka, MD: I have a lot of optimism, but cautious optimism. They look very positive in terms of efficacy, and they essentially included patients who had failed to respond to other therapies, so it really might target that population who has the most need. My hesitation is in the presentation description that they have—it is almost side-effect free. Each of these trials has only included a few thousand patients and so it’s been a really small number of people that’s been exposed to medications, and I’m hopeful they will pan out to be as safe as they currently look, but I think we really need more data before we can conclude that. I want to see more data from the population in general, regardless of age.
Then, obviously, we’ll need more information on what the effects of these medications are on a pre-pubertal child. Sometimes we will have 9-year-olds who have failed multiple different therapies. Would I reach for in the CGRP antibodies in that circumstance or not? We have a lot of questions and not a lot of answers there.
To my knowledge, there’s one pharmacokinetics study that’s enrolling, one that’s about to start, and that’s it. So, we’re still pretty far out, I think, from the point of actually getting substantial data. Now having said that, most of what we’ve done in pediatrics, historically, has been off label. Because it’s only in the past 15 years, with the different changes in the laws, that there have been pediatric trials. Most of what we’ve done in the past has been all off-label. I could prescribe it off-label it’s just that there’s hesitation about doing that.
For acute therapies, it was realized many years ago that the standard parallel design study—so randomized to this group and that group—was not resulting in a demonstration of efficacy. So, the trials became more nuanced and with that several of the triptans were demonstrated to have a clear response and are now FDA approved. So, from an acute therapy standpoint it seems like that’s really been worked out, but it seems like we need to do either a placebo lead-in or a crossover design to maximize the chance that you’ll find the benefit, if it really exists.
For preventive therapies we’re just getting there. The CHAMP trial of amitriptyline and topiramate versus placebo, a multisite, NIH-funded trial, demonstrated about 60% of children in each group had a positive outcome that had a 50% reduction in their headache frequency. It was a very positive trial, because it demonstrated what we’re doing in standard of care is really effective in most kids. But it didn’t split out from placebo and that made us question, “OK, how are we doing this?”
Since then, the trial of onabotulinum toxin A in adolescences, which was a parallel design study and started around the same time as the CHAMP study, completed about a year or so ago, and that one did not demonstrate efficacy. Having said that, many of us use onabotulinum toxin A for patients, because we find that it’s really effective for some kids. I think that’s a demonstration of the fact that if it had been done with a more nuanced trial design, perhaps we would have seen something.
As we move into newer therapies, that becomes the question. I have a colleague who is doing a trial of one of the nutraceuticals and is using a placebo lead-in design for that preventive trial because, again, we learned from CHAMP that we need to do something. That’s part of the research question, really. Can this placebo lead-in design help to demonstrate efficacy?
In terms of the CGRP trials, to my knowledge, some of them started planning before the CHAMP study came out. So, I’m not sure if they’re going to be using the old parallel design or something like a placebo lead-in. If they permit enrollment of kids that are already refractory that may also help the problem, because as I said in the adult trials those patients do respond, and actually those patients who are refractory look like they had an even clearer response compared to placebo. So, in the CGRP trials if they’re not doing something that’s placebo lead-in, if they have a number of patients that are refractory already to other meds that may help the problem.
Transcript edited for clarity.