The oral treatment, marketed as Rizafilm, is a disintegrating film formulation of the 5-HT1 receptor agonist and is bioequivalent to Merck’s Maxalt-MLT.
The FDA has approved IntelGenx/Gensco's rizatriptan benzoate (Rizafilm VersaFilm) oral thin film for acute migraine treatment through the 505(b)(2) new drug application (NDA) pathway. This newly approved treatment is an orally disintegrating film formulation of the 5-HT1 receptor agonist designed to be bioequivalent to Merck’s Maxalt-MLT, an orally disintegrating rizatriptan treatment.1
Brian Grosberg, MD, FAHS, a headache specialist and the medical director of the Hartford Healthcare Headache Center, in Connecticut, told NeurologyLive® that, "the FDA approval of Rizafilm makes available another acute treatment option for migraine which may offer rapid relief and improvement of migraine, especially in those who experience nausea."
The treatment's bioequivalence was established in a single-dose, randomized, open-label, 3-way crossover, pivotal, comparative bioavailability study of Rizafilm 10 mg, Maxalt-MLT 10-mg orally disintegrating tablets, and Maxalt-Lingua 10-mg orodispersible tablets in 30 healthy volunteers. The study was conducted under the direction of Biopharma Services in Toronto, Ontario, Canada. The equivalence was announced in late 2018 by IntelGenx.2
The study was designed to determine whether the product is safe and bioequivalent to a leading anti-migraine product as measured by industry-standard pharmacokinetic measures, peak plasma concentration (Cmax), and area under the curve (AUC). The study results indicated that the product was safe and that the 90% confidence intervals of the 3 parameters of Cmax, AUC(0-t), and AUC(0-infinity) were well within the acceptable 80 to 125 range for bioequivalency.
In December 2018, IntelGenx and Gensco went into a definitive licensing, development, and supply agreement for the exclusive commercialization of Rizafilm in the US.1 The treatment was previously approved in the European Union under the trade name Rizaport.
“Following a successful preapproval inspection by the FDA of our Montreal manufacturing facility earlier this month, we are thrilled to reach this milestone and excited to soon introduce what will be the first oral thin film for the treatment of acute migraines available in the US,” Andre Godin, IntelGenx’s president and CFO, said in a statement.1
Previously, in March 2020, the FDA issued a Complete Response Letter (CRL) to IntelGenx for its NDA for the Rizafilm VersaFilm formulation.3 The agency had requested IntelGenx provide additional information, but not a new bioequivalence study. Thus, IntelGenx planned a meeting with the agency to discuss the comments from the CRL with the goal of gathering the necessary clarification and determining the next steps.
Then, in April 2020, IntelGenx announced various initiatives targeted to help the company address and respond to the CRL from the FDA regarding its resubmitted 505(b)(2) NDA for the treatment.3,4 In May 2020, the FDA granted IntelGenx a request for a Type A meeting regarding its treatment, scheduled on June 10, 2020.4,5
After the meeting, the company provided an update and obtained clarity from the FDA on the Chemistry, Manufacturing and Controls (CMC) information required for the remission of the NDA. In October 2022, IntelGenx responded to the CRL, after the agency declared it could not approve its application in its current form.6 In November 2022, the FDA accepted the Class 2 response for review and set a new PDFUA target action date.7
This treatment now joins a growing list of new options for migraine that have earned FDA approval in the past 5 years—including a number of other additional formulations of agents aimed at circumventing administration challenges. This includes as recently as last month, when the FDA gave the go-ahead of zavegepant nasal spray (Zavzpret; Pfizer) for the acute treatment of migraine with or without aura in adults. That therapeutic became the first and only calcitonin gene-related peptide (CGRP) receptor targeting nasal spray available for patients with migraine.