To follow up on the exciting discussions that took place at this year’s American Headache Society Conference, we spoke with Peter Goadsby, MD, PhD, FAHS, AHS Scientific Program Committee Chair on the new class of treatment options for migraine.
How are CGRPs different from other preventatives?
Several ways. First, these will be migraine preventatives that are designed for migraine. Everything else we use came from medications that were originally indicated for a different disorder such as epilepsy or depression, and those medications come with baggage of side effects. Secondly, they block the CGRP and block the receptor, there’s no question about their target. CGRP plays an important role in migraine and these new treatments are specifically for this mechanism. Thirdly, CGRP-directed treatments are very well tolerated. Apart from 5% reporting skin irritation with the injection, nothing else has emerged from the side effect profile compared to the placebo. This would be a reassuring result from one large program – but there have been four multisite trials so that quadruples the reassurance. With current treatments we see variations on cognitive dysfunction, weight gain, dry mouth, or sleeping issues but none of those side effects were seen. This is a big difference no matter how you look at it.
In the past, antibodies were used to manipulate to respond more or respond less, so-called immune modulation. Now, the CGRPs take out the desired target, CGRP, without any effects on the immune system. The immune part of the molecule has been engineered out; it is a very important distinction for these new treatments.
How do you foresee the availability of CGRPs changing the migraine treatment options?
It will be an important addition. I don’t think giving it to everyone with migraine will happen anytime soon. However, the new treatments will provide options to people who have failed or not tolerated standard preventatives. It will be preferable to try the CGRPs before, for example any implantable neuromodulation approaches. We won’t stop tomorrow afternoon using the older medicines; although for any person who has years of getting nowhere on old medicines, it will be a huge difference when these are available.
What limitations can patients expect?
From a medical perspective, if you’re asking who is a candidate the answer would be episodic and chronic migraine patients who have disabling migraine and in whom orthodox preventives have not worked. Patients who were using Botox in the previous months were excluded to test the efficacy of CGRPs, but in practice, that would not be a limiting factor. Who is a poor candidate? Well it’s not obvious yet because no problems have arisen. It’s much trickier to say who won’t be a good candidate. Once it’s in practice, there may be a broader view in balancing risk/benefit. In clinical trials, we have not observed risks but we did observe a reduction in disabling migraine. That is such new territory.
Do you think CGRP development will lead to more focus on developing additional migraine treatment options?
I’m trying to get younger physicians involved. I think they are getting more interested in neurology and headache disorders – they’re heading in the right direction, but I would like it to head there faster.
I think it’s an exciting time. Initially, CGRPs will be offered as subcutaneous injections or intravenously administered. Allergan has Phase II clinical trials for oral form of a CGRP blocker, a tablet. One of the good things about having success is it teaches people that success is possible, that there are a lot of people with migraine, and a lot opportunities. The road map will lead to research growth.
What should a patient’s realistic expectations be?
If you look across the range – a realistic expectation is 40-50% of people with migraine will have a 50% reduction in their migraine. Half the people with migraine will have it halved. If you’re in the glass half full mode, 20-30% of the participants in the clinical trials had a 75% reduction in their migraine days. For 10-15% of the participants, their migraine days went away all together.
To communicate the data would show half of the people saw great improvement. Cautious but real optimism is a good way to look at this.
For more on migraine, visit the American Migraine Foundation.