Intranasal DHE delivery system safe, effective against migraine in phase 3 trial

Biotech company Impel Neuropharma announced that its precision olfactory delivery device, or POD, safely delivered the company’s nasal dihydroergotamine-based INP104 treatment to patients with migraine.

The results of the phase 3 trial were presented recently during the virtual PAINWeek meeting.

Dihydroergotamine, or DHE, first became available as an acute migraine treatment in the 1940s. DHE’s cumbersome administration and the popularity of oral migraine treatments limited its acceptability among consumers, according to experts. In recent years, researchers have studied the effectiveness of DHE formulations such as INP104 (Impel Neuropharma) and STS101(Satsuma Pharmaceuticals).

“We have previously shown that administering 1.45 mg of DHE via the POD to the upper nasal space generated plasma levels similar to 1 mg DHE administered intravenously within 20 minutes to 48 hours,” Sheena K. Aurora, MD, vice president of medical affairs in Impel Neuropharma’s migraine division, said during the presentation.

For the new trial, 360 adult patients with migraine were enrolled in a 28-day screening period, during which they received “best usual care.” Over the next 24 weeks, they were given a maximum of three doses of INP104 per week (one dose = two puffs totaling 1.45 mg) to self-administer using the POD. According to Impel Neuropharma’s website, patients can either squeeze finger grips on one version of POD to administer a liquid form of the drug or push buttons to receive a powder form of the drug.

Researchers wrote that there were 4,515 migraines among the participants. Within 2 hours of receiving INP104, 33.1% of all patients reported freedom from migraine pain without the use of rescue medication, 49.1% had comfort from their most bothersome migraine symptom and 66.3% had pain relief. About 84% of patients found INP104 easy to use and preferred it over their current therapy.

Freedom from pain was sustained over 24 hours in most patients, 98.4% of whom were relapse-free of migraine after using INP104 from weeks 21 to 24 vs. 93.2% using “best usual care” at baseline.

The most common treatment-related adverse events were nasal congestion (15%), nausea (6.8%) and nasal discomfort and unpleasant taste (5.1% each), according to the researchers. All other treatment-related adverse events, none said to be serious, were reported by less than 3% of participants.

“No new safety signals were reported with the use of DHE when delivered to the upper nasal space,” Aurora said. “Tolerability, patient acceptability and expiratory efficacy results were encouraging.”

Impel Neuropharma said that it intends to file a new drug application for INP104 no later than 2021.

References:

• Impel Neurophama. Our science. https://impelnp.com/our-science/. Accessed Sept. 14, 2020.
• Impel Neurophama. Pipeline. https://impelnp.com/treatments/. Accessed Sept. 14, 2020.
• Impel Neuropharma. Presentations. https://impelnp.com/2020/06/13/patient-acceptability-of-a-novel-upper-nasal-delivery-system-for-dihydroergotamine-mesylate-using-the-precision-olfactory-delivery-pod-device-results-from-the-open-label-stop-301-trial/. Accessed Sept. 14, 2020.
• Impel Neurophama. STOP 301: Open-label safety and tolerability of chronic intermittent usage for 24/52 weeks of INP104 [nasal dihydroergotamine mesylate (DHE) administered by Precision Olfactory Delivery (pod®) device] in migraine headache. https://impelnp.com/2019/08/05/stop-301-open-label-safety-and-tolerability-of-chronic-intermittent-usage-for-24-52-weeks-of-inp104-nasal-dihydroergotamine-mesylate-dhe-administered-by-precision-olfactory-delivery-pod-de/ Accessed Sept. 14, 2020.