20 Feb CGRP: What You Need to Know – Clinical Trials
By Dr. James Banks, National Headache Foundation Board Member
This is the second part of a series related to CGRP. In the first part of the series, Dr. James Banks looks at the basics of CGRP and how it works.
Where are CGRP agents currently in the trial process and what are the early results?
The four companies with the most advanced research on the CGRP antagonists are, in alphabetical order, Alder, Amgen, Eli Lilly, and Teva. Amgen (in conjunction with Novartis) is currently involved in research on an oral CGRP antagonist. At www.headaches.org and www.clinicaltrials.gov, you’ll find a listing of where, who and what is being studied.
Participation in a clinical research trial is different from the usual doctor-patient relationship. There are strict criteria for who qualifies and what can be done. Most trials do not promise that you’ll receive the experimental treatment, but some later trials (Phase III) often contain a prolonged period of “open-label” treatment. This period is when the subject and researcher know that the patient is receiving the actual experimental treatment and at what dose.
All studies considered (published and yet to be published but reported at scientific meetings) have shown statistically significant improvement in reducing the number of headache days per month compared to placebo (a non-active substitute). These results reflect both the episodic migraine, as well as chronic migraine populations. Also, the CGRP antagonists are noted to reduce the impact of migraine on health-related quality of life measures; decreased utilization of acute, abortive medications; and, decreased urgent/emergent healthcare visits.
For chronic migraine patients, 30 to 50% of subjects had greater than 50% reduction in number of headache days per month. A small percentage experienced complete relief from their headaches and some noted the effect within one week, and most within one month of treatment. This effect appears to be prolonged, and maintained through the observational periods. Several resources are available for more detailed information regarding the results and analyses from these studies.
How do these results compare to other migraine treatments, such as triptans or onabotulinumtoxinA?
Triptans were developed to reverse (stop the process of migraine once it has started). The triptans were discovered at a time when we believed migraine was primarily a blood vessel and nerve problem. From the start of the process, small molecule CGRP antagonists have been studied as oral migraine abortive and preventive therapy with demonstrated efficacy. However, there are some concerns of liver toxicity.
Research using various triptans for preventing migraines have generally shown that this class of medications should be reserved for acute, abortive therapy. The exception is frovatriptan (Frova), a particularly long-acting triptan, that is used in some cases of predictable menstrually-related migraines as a short-term preventive therapy.
OnabotulinumtoxinA (Botox) is the only treatment approved specifically for treating chronic migraine. But the development of Botox was for other conditions. It was only researched because of patients on Botox therapy for other reasons reporting that it reduced their headaches.
Clinical trials using Botox for chronic migraine prevention in a highly impacted patient population has shown that generally, patients suffering with 23 to 24 days a month of migraine at baseline experience a reduction of only 3 to 5 days a month with treatment. Additionally, disruption to their daily lives is reduced by a third, and quality of life measures are markedly improved. Quality of life measures were also markedly improved.
As these were highly impacted individuals, the improvement was sufficient for the FDA to approve onabotulinumtoxinA for treatment of chronic migraine.
The CGRP antagonist data was not as robust as expected by headache researchers; however, the results are better than Botox. Likewise, quality of life improvement has been quite remarkable for CGRP antibodies.
Botox requires 31 injections (albeit very tiny ones) around the head, neck, and shoulders. Roughly 2 to 5% of patients experience noticeable weakness, or paralysis of muscles after treatment (reversible), and the majority experience pain, irritation, or redness with the injections. Thus, the CGRP-antagonists are considered (at this point in time) to be much better tolerated.