Rimegepant Application for Migraine Prevention Accepted for Review

October 14, 2020

If approved, rimegepant will be the first and only anti-CGRP agent indicated for both the preventive and acute treatment of migraine.

Biohaven Pharmaceuticals has announced that its supplemental new drug application (sNDA) for rimegepant (Nurtec ODT) for the prevention of migraine has been accepted by the FDA, with a planned Prescription Drug User Fee Act (PDUFA) action date set for the second quarter of 2021.1

The orally disintegrating anti-calcitonin gene-related peptide (CGRP) tablet was originally approved in a 75-mg dose for the acute treatment of migraine in February 2020, marking the first approval for Biohaven.2 If approved for this second indication, rimegepant will be the first and only CGRP-targeting therapy with indications for both preventive and acute treatment of migraine.

The basis of this new sNDA is built on data from the company’s pivotal study—known as Study 305—in migraine prevention, which showed the same dosage was associated with a significant 4.3-day reduction in monthly migraine days.1

“Patients with migraine deserve the simplicity of managing their disease with a single medication that alleviates acute episodes and also works to prevent future attacks. Our goal with the Nurtec ODT development program has been to offer a fast-acting, quick-dissolve oral tablet with ‘dual-acting’ properties—acute and preventive—to treat migraine across its full spectrum,” said Vlad Coric, MD, chief executive officer, Biohaven, in a statement. “We believe that the ease of use associated with a single oral medication will benefit people with migraine so that they can take back their days, and also provides the health care system with a cost-effective approach as opposed to paying for two separate drugs for acute and preventive treatment.”

Study 305 included 348 patients with migraine randomized to receive 75-mg every other day and 347 patients on placebo. All told, those on rimegepant experienced the aforementioned 4.3-day reduction from baseline compared to the placebo group’s 3.5-day reduction (difference, 0.8; P <.05). Notably, of those in the rimegepant group, 49.1% reported a ≥50% reduction from the baseline number of moderate to severe migraine days compared to 41.5% in the placebo group (P <.05).

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Additionally, the sNDA is supported by data from the long-term, open-label safety study, Study 201, which was included in the original NDA for rimegepant’s acute treatment indication. That study included 1800 participants who used the agent once per day, including 1131 individuals who were exposed to the drug for at least 1 year. Every patient included in the 1-year data treated a mean of 2 migraine attacks per month.

“Unlike the injectable CGRP-targeting biologics, Nurtec ODT offers the potential for a convenient oral medication with dual benefits for both the acute and preventive treatment of migraine, requires no injection, and has a half-life of approximately 11 hours that allows immediate cessation of therapy in the event of pregnancy, nursing, hypersensitivity reaction, or adverse reactions,” said Elyse Stock, MD, chief medical officer, Biohaven. “Thus, NURTEC ODT's safety and efficacy has the potential to address important unmet needs in the current landscape of preventive treatments of migraine.”

In April 2020, Biohaven announced that rimegepant became available for prescription via telemedicine after a collaboration with Cove, which focuses on providing specialized care and access for patients with migraine. Biohaven noted that this collaboration is hoping to facilitate telemedicine evaluation for this population, particularly in the midst of the COVID-19 pandemic and an increased need for virtual visits. The collaboration makes the oral agent the first branded medication available through Cove’s platform, which allows patients to consult with independent health care providers and may be prescribed migraine treatments.3

Additionally, in August this year, new safety data published in Headache suggested that rimegepant can be safely administered in tandem with the preventive monoclonal antibodies against CGRP. At least 1 on-treatment adverse event (AE) was reported by 38% (n = 5), after a mean 4-week exposure of 7.8 doses (standard deviation [SD], 5.5; total, 224 doses). Of those, 15% (n = 2) of the patients had mild or moderate nasopharyngitis; no other AEs occurred in ≥2 patients. Possible treatment-related AEs of mild to moderate severity— viral gastroenteritis, first-degree atrioventricular block, and dizziness—occurred in 23% (n = 3) of patients. Notably, no patients had serious AEs, AEs leading to discontinuation, or aminotransferase levels >3 times the upper limit of normal. Of the 12 patients with liver function test data, 1 patient had an AST level that was above normal (45 U/L; 1.1× ULN).4

Those data were pulled from a substudy within a multicenter, open-label, long-term safety assessment of adults with episodic migraine (2—14 days per month) of moderate to severe pain intensity (NCT03266588). A subgroup of patients experiencing 2–8 monthly attacks and taking a stable dose of a CGRP monoclonal antibody also took 75-mg rimegepant as needed up to once daily for acute treatment for 12 weeks.4

REFERENCES
1. U.S. FDA Accepts Biohaven's Supplemental New Drug Application (sNDA) Of NURTEC™ ODT For The Preventive Treatment Of Migraine. News release. New Haven, CT. Biohaven. Published October 14, 2020. Accessed October 14, 2020. biospace.com/article/releases/u-s-fda-accepts-biohaven-s-supplemental-new-drug-application-snda-of-nurtec-odt-for-the-preventive-treatment-of-migraine
2. Biohaven's NURTEC™ ODT (rimegepant) Receives FDA Approval for the Acute Treatment of Migraine in Adults. News release. New Haven, CT. Biohaven. Published February 27, 2020. Accessed October 14, 2020. prnewswire.com/news-releases/biohavens-nurtec-odt-rimegepant-receives-fda-approval-for-the-acute-treatment-of-migraine-in-adults-301013021.html
3.Biohaven Enters Into Collaboration With Cove, Leading Migraine Telemedicine Platform, To Enhance Accessibility Of NURTEC™ ODT. News release. New Haven, CT. Biohaven. Published April 7, 2020. Accessed October 14, 2020. prnewswire.com/news-releases/biohaven-enters-into-collaboration-with-cove-leading-migraine-telemedicine-platform-to-enhance-accessibility-of-nurtec-odt-301036378.html
4. Berman G, Croop R, Kudrow D, et al. Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine. Headache. Published online August 16, 2020. doi: 10.1111/head.13930.