Updated STOP 301 results demonstrate safety, tolerability of INP104 for migraine
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Updated analyses from the phase 3, open-label STOP 301 study of nasal dihydroergotamine-based INP104 for the treatment of migraine provides new safety and tolerability data regarding nausea as well as nasal and cardiovascular outcomes.
Researchers presented the findings at the American Headache Society Virtual Annual Scientific Meeting.
“New safety and tolerability analyses of STOP301 data will include findings on nausea, as well as nasal and cardiovascular safety,” Carrie Dougherty, MD, FAHS, associate professor of neurology at MedStar Georgetown University Hospital, told Healio Neurology.
Researchers initially all followed participants for 4 weeks, during which time they used “their best usual care” to manage migraines. After completing the screening period, participants received up to 3 doses per week of INP104 to nasally self-administer. The dose of INP104 was 1.45 mg delivered in two sprays, one in each nostril, according to the study results.
The trial included 354 patients treated with INP104 in the full safety set. Investigators collected results regarding nausea and nasal treatment-emergent adverse events over 52 weeks and collected results related to cardiovascular events over 24 weeks.
Results related to nausea demonstrated that, while nausea is “widely reported” after IV administration of dihydroergotamine mesylate, patients treated with INPO104 in the STOP 301 trial did not require pretreatment with an antiemetic. Additionally, less than 1% of INP104 doses led to nausea, and only 0.8% of treated patients withdrew from the study because of a treatment-emergent adverse event related to nausea.
“This study demonstrates the possibility for a lower incidence of the self-limiting treatment-emergent adverse event of nausea, with the potential to offer a viable delivery alternative to dihydroergotamine mesylate users,” the researchers wrote.
Additionally, findings related to nasal safety demonstrated mild to moderate mucosal edema in 5% of patients on endoscopy, though the researchers noted that this “was not considered a concerning finding.” Most subclinical cases of olfactory reduction in patients with nasal treatment-emergent adverse events resolved, according to the study results (14/17). Monitoring for nasal adverse events demonstrated that a limited percentage of patients developed nasal discomfort and congestion that led to treatment discontinuation during the 24-week study period (1.1% and 1.4%, respectively).
Finally, the analysis from the STOP 301 trial of INP104 showed no significant adverse events in the peripheral or cardiovascular systems, even among patients with cardiovascular risk factors or those with concomitant triptan use, though the researchers did note that patients with active cardiovascular disease were omitted from the study. Patients who received INP104 exhibited few treatment-related adverse events and no treatment-related cardiac events, according to the study results.
“These analyses further support the clinical profile of investigational INP104 and demonstrate that INP104 may be a promising new acute treatment for migraine attacks,” Dougherty said.
The FDA set a PDUFA date of Sept. 6, 2021, for INP104. If approved, INP104 would be marketed under the trade name Trudhesa in the United States, according to a press release issued previously from Impel NeuroPharma.
References:
Craig K, et al. Cardiovascular safety results of INP104 (POD-DHE) from the STOP 301 phase 3 study. Presented at: American Headache Society Annual Scientific Meeting; June 3-6, 2021 (virtual meeting).
Davis G, et al. Nasal safety of chronic intermittent use of INP104: Results from the phase 3 open-label STOP 301 study. Presented at: American Headache Society Annual Scientific Meeting; June 3-6, 2021 (virtual meeting).
Impel NeuroPharma. Impel NeuroPharma announces U.S. Food and Drug Administration acceptance of new drug application for INP104 for the acute treatment of migraine. Available at: https://impelnp.com/2021/01/20/impel-neuropharma-announces-u-s-food-drug-administration-acceptance-of-new-drug-application-for-inp104-for-the-acute-treatment-of-migraine/. Accessed June 4, 2021.