Phase 3 Clinical Trials’ Data on Oral CGRP Presented at AHS
The American Headache Society (AHS) hosted its Annual Scientific Meeting this past week, which included several late-breaking presentations from Biohaven Pharmaceutical Holding Company Ltd. Biohaven is in the process of testing their new, orally-administered CGRP receptor antagonist, rimegepant, and presented some promising results on the drug’s ability to provide individuals living with migraine with relief. Data from two Phase 3 clinical trials were presented, as well as additional data on rimegepant’s effect on vasoconstriction and its ability to be manufactured as an orally dissolving tablet (ODT).1
What is a CGRP receptor antagonist?
CGRP (calcitonin gene-related peptide) is a protein thought to be involved in several pain response pathways within the brain and body. It acts as a chemical messenger within the body and transmits signals on sensations like pain. CGRP is considered a neurotransmitter. It also impacts blood vessels and is found in high levels during a migraine attack. New medications have been in development to block CGRP and its receptors, called receptor antagonists, in order to potentially stop migraine attacks related to this protein and its related processes in the body. The first FDA approved CGRP inhibitor, Aimovig, was approved this past May and is administered as a once-monthly self-injection.1,2
What do the data from the clinical trials show?
The two Phase 3 clinical trials of rimegepant included over 1,000 individuals with migraine each, and tested the effects of rimegepant against a placebo. Both studies met their co-primary endpoints of freedom from the most bothersome migraine symptom and pain freedom two hours after taking rimegepant. These effects were tested longer-term, and were found to still be present between two to 24 hours and two to 48 hours post-administration of rimegepant. Functional disability was also decreased two hours after taking rimegepant, and continued to be present when compared to placebo across the 24 and 48 hour periods. Significant relief from migraine related symptoms, such as nausea, light sensitivity, and sound sensitivity, was also found when compared to placebo in the first eight hours after treatment with rimegepant.
The safety profile of rimegepant was found to be similar to placebo, and the most common adverse effect of the medication was nausea, with less than 2% of individuals experiencing this side-effect. It was also found that those taking a single dosage of rimegepant were less likely to need to use an additional rescue medication when compared to their placebo-receiving counterparts.1,3,4
Other results presented
In addition to the results from the Phase 3 clinical trials presented, Biohaven also delivered two other presentations related to rimegepant. The first of these investigated rimegepant’s effect on the blood vessels. A common treatment for migraine, triptans, constrict the body’s blood vessels, and thus, are not indicated for everyone, especially those with cardiovascular conditions or who are at high risk of developing a cardiovascular complication. Biohaven tested rimegepant’s effect on the body’s blood vessels to determine if it is safe for individuals with cardiovascular issues to use rimegepant. Rimegepant did not show any evidence of vasoconstriction (constriction of the blood vessels), whereas sumatriptan (a triptan medication) did constrict the blood vessels. These results may indicate that individuals who previously could not take triptans due to cardiovascular concerns may be able to take rimegepant.5
The final study presented was a Phase 1 study on the administration of rimegepant. The current CGRP antagonist on the market is injectable, and rimegepant is orally administered, meaning it may be easier or more convenient to take. Additionally, Biohaven used data on the preferences of individuals with migraine and determined that these individuals may be interested in having an orally dissolving tablet (ODT) that is even more convenient to take and that may have a more rapid onset of action. Biohaven tested if a new orally dissolving version of rimegepant was equivalent to the orally administered non-dissolving tablet, and if the dissolving version had a faster time to peak blood concentration of rimegepant. Their study showed that at the Phase 1 level, both types of rimegepant were found to be bioequivalent and that the rimegepant ODT may have a faster onset of action. Currently, a Phase 3 clinical trial on the rimegepant ODT is underway.6
Biohaven is also initiating a Phase 3 clinical trial before the end of 2018 that will investigate rimegepant’s use as a potential preventative treatment of migraine in addition to being an acute treatment of the disease.1
These results and announcements indicate that the orally-administered CGRP antagonist rimegepant may be a promising migraine treatment option in the near future.
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