A key opinion leader illustrates how recently approved rimegepant for preventive episodic migraine treatment could change the treatment landscape.
David Kudrow, MD: How would I expect the recent approval of rimegepant for the preventive treatment of episodic migraine to change the treatment landscape? This is an interesting question. For decades, we’ve been thinking about migraine therapeutics in terms of acute and preventive migraine treatment. Those 2 concepts never converged until recently. As we all know, rimegepant was approved by the FDA for the treatment of acute migraine about a year ago. I may be off a little, because the pandemic has thrown off my sense of time. In any case, it was initially approved for the acute treatment of migraine in patients with and without aura.
As an investigator involved in those clinical trials, in the long-term safety studies, patients would be given a bottle of 30 rimegepant and told, “Use it on an as-needed basis, provided you don’t take it more than once per day.” Patients would come back for their study visits monthly and say, “It’s interesting. It works very well for my acute migraine, but I’m also having fewer migraines or fewer migraine days.” A study was subsequently done looking at rimegepant 75 mg for the preventive treatment of migraine, and the dosing schedule was every other day. Why? Because in the acute studies, it showed a pretty good, sustained pain relief or pain freedom from 2 hours to 24 and even 48 hours. It also has a relatively long half-life for an acute migraine treatment of up to about 11 or 12 hours. That’s the reason for the dosing schedule. Subsequently, a double-blind placebo-controlled preventive study was done with rimegepant, and it showed efficacy vs placebo in reducing migraine days over 12 weeks.
The interesting concept that we’re now dealing with is that we’re using an acute medication for both the acute treatment of migraine and also the preventive treatment of migraine. That throws us off or blurs the lines between our traditional thinking about migraine therapeutics. In terms of reduction in mean monthly migraine days, a greater proportion of patients on rimegepant had 50% or better reduction in monthly migraine days as well. But as a specialist, it’s making me think, “How do I use this medication?” Another interesting attribute of the CGRP antagonist class is that they don’t seem to cause medication overuse or rebound headaches, which means the patients could theoretically use them on an as-needed basis without having to worry about precipitating medication overuse headache.
I’m now thinking about where the medication is appropriate. If patients want to use it on an as-needed basis as much as they want, that should be OK. If patients want to use it on a preventive basis to ensure that they don’t have migraine attacks, or at least have a reduction in the frequency of migraine attacks, that’s OK, too. If they want to use it on a preemptive basis, such as for an anticipated event that they know will trigger a migraine—perhaps menstrual migraine—then they can use it preemptively as well. The introduction of rimegepant as an acute and preventive treatment for migraine has changed the way we see migraine therapeutics, or at least the way we’ve traditionally looked at migraine therapeutics.
Another aspect that’s important is that we now have injectable monoclonal antibodies among this large class of CGRP antagonist medications, and we have the small-molecule CGRP antagonists. The monoclonal antibodies have a very long half-life of 27 to 31 days. In a population of patients with migraine who are predominantly female and of child-bearing potential, we have to be cautious about using drugs that have very long half-lives, particularly in women who aren’t committed to not becoming pregnant while on the medication.
We don’t know what the effect is on pregnancy or the developing uterus. We have to be cautious. I’m very cautious about using those medications in women of childbearing potential and want to make sure there’s a strategy or commitment to not become pregnant while they’re on the medication because of the long half-life. Traditionally, we say patients should wash out the medications, and it should take 5 half-lives. That’s 5 or 6 months. On the other hand, ubrogepant, a small-molecule CGRP antagonist similar to rimegepant, has a much lower half-life. In 2 days or 2 and a half days, the medication should be entirely out of their system. In that population of patients, it’s a consideration that a medication with a shorter half-life might be a reasonable option in someone who may become pregnant while on the medication. They can wash out the medication very quickly if necessary.
Transcript edited for clarity.