Biohaven’s small molecule CGRP receptor antagonist rimegepant has displayed safety and efficacy in a small cohort of patients with migraine using it alongside erenumab.
Kathleen Mullin, MD
Recently published data from 2 patients with migraine experiencing suboptimal response to medication suggests that concomitant use of rimegepant (Biohaven) and erenumab (Aimovig; Amgen) can effectively treat refractory migraine.1
The work, conducted by Kathleen Mullin, MD, medical director, clinical research, New England Institute for Clinical Research, and colleagues, is the first clinical report documenting that 2 calcitonin gene-related peptide (CGRP) therapies can be used this way.
Although the data are an exciting first step, Mullin and colleagues noted that “the mechanism underlying the benefits of concomitant use of a small molecule CGRP receptor antagonist and an anti-CGRP receptor antibody is unknown and requires further study.”
“There's something to be said—if you think about it, these are patients that respond to the monoclonal antibodies as their preventative,” Mullin told NeurologyLive
. “If these patients that we put on CGRP monoclonal antibodies have a successful reduction in the monthly migraine days—what we call CGRP responders—then why wouldn't something that sort of further suppresses that pathway in an acute way be effective for them to abort their migraines as they come?”
Many physicians have speculated this, given the mechanistic similarities between the oral agents and their injectable counterparts. Most importantly, as many physicians, including Mullin, have noted, the preventatives, while effective at reducing monthly migraine days, are not cures for migraine.
“These patients will still need an acute treatment. It might be something that we look at—if the patient's responses to something that blocks their CGRP receptor as a preventive, why wouldn't we then further look at that same pathway for their acute treatment?” Mullin said.
The study included 2 patients in a long-term safety study of the small molecule CGRP receptor antagonist rimegepant who began taking the anti-CGRP receptor antibody erenumab subcutaneously once it was granted FDA approval. Both patients were women (patient 1, age 44 and patient 2, age 36) with ≥20 years of suboptimal response, per self-reports. Neither patient reported any adverse events (AEs).
Patient 1 used rimegepant for 6 months prior to initiating 70 mg erenumab monthly. She responded to preventive treatment, and additional as-needed use of rimegepant successfully quelled 100% (n = 7) of her acute attacks. Additionally, it eliminated regular, frequent use of ibuprofen and a caffeinated analgesic.
Patient 2 had used rimegepant for 60 days before beginning 140 mg erenumab monthly. Similarly, 100% (n = 9) of her acute attacks treated with rimegepant were successful. She halted “near-daily” use of injectable ketorolac and diphenhydramine as well.
“What was nice to see was that these patients were on rimegepant before they were on erenumab,” Mullin said. “At least my patient said that—subjectively—she actually thought rimegepant worked better when it was used conjunctively with the monoclonal antibody. That was, again not necessarily surprising, but reassuring and nice to see that they may even have sort of a synergistic effect.”
Mullin told NeurologyLive
that Biohaven has been working to gather safety and efficacy data on the use of the available CGRP monoclonal antibodies alongside rimegepant.
Notably, she and colleagues detailed that Biohaven will provide access to de-identified patient-level data underlying the results of this publication “in response to scientifically valid research proposals.” The data from this study should be made available 9 months after its publication and ending 24 months later.
Biohaven submitted a new drug application to the FDA for rimegepant in the second quarter of 2019, with a PDUFA date upcoming in the first quarter of 2020.2
1. Mullin K, Kudrow D, Croop R, et al. Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy. Neurology. 2020;00:1-5. doi:10.1212/WNL.0000000000008944.
2. Biohaven's Rimegepant for Migraines Heads to the FDA for Approval Following Successful Trial [press release]. New Haven, CT: Biohaven; Published July 11, 2019. biospace.com/article/biohaven-s-migraine-drug-shows-superiority-for-freedom-from-pain-in-phase-iii/Accessed January 14, 2020.