A long term, open label study of Safety and Tolerability Of Precision olfactory delivery of DHE in acute migraine (STOP 301): Clinical Results

Presented at the 2020 PAINWeek Live Virtual Conference

Authors: Sheena Aurora, Maria Jeleva, Jasna Hocevar-Trnka, John Hoekman, Stephen Shrewsbury

Introduction:

Migraine is a common neurological disease impacting at least12% of the United States population. Despite several recent approvals of novel abortive treatments, a high unmet need and patient dissatisfaction remains for early onset of effect, sustainable pain relief, and reduced recurrence of migraine attacks. Systemic dihydroergotamine (DHE) mesylate has a rapid onset and sustained effect, and we have previously reported similar plasma levels of DHE mesylate from 20 minutes achieved with INP104 in our Phase 1, STOP 101 trial. INP104 is a novel drug-device combination product that targets delivery of DHE mesylate to the upper nasal space, a previously unexplored route of administration, using a Precision Olfactory Delivery (I123 POD ® ) device.

Objective:

To report the safety, tolerability, patient acceptability and exploratory efficacy of INP104 for migraine from the pivotal, Phase 3 STOP 301 trial.

Methods:

STOP 301 was a multicenter, open-label, 24-week safety, tolerability, patient acceptability and exploratory efficacy study, with a subset entering a 28-week extension period (52-week treatment); (NCT0355733). Patients were required to complete a daily diary and a migraine diary with every attack during screening period and on treatment. After a 28-day screening period where patients used their “best usual care” to treat migraine attacks, patients were allowed to self administer up to 3 doses/week of INP104 nasally with self-recognized migraine attacks (1.45 mg in 2 puffs through the POD device). The primary objective of this study assessed safety and tolerability, with specific focus on change in nasal mucosa and olfactory function. Exploratory objectives included efficacy assessments of migraine measures compared to best usual care, patient acceptability by a questionnaire (PAQ), and healthcare
utilization and quality of life measures (MIDAS and HIT-6) were also collected.

Results:

360 patients entered the 24-week treatment period, with 185 and 354 patients in the Primary Safety Set (PSS) and Full Safety Sets (FSS) respectively, while 55 and 73 patients composed the respective 52-week data sets. 36.7% of patients reported AEs, with 6.8% of patients discontinuing due to AEs (FSS). No significant olfactory mucosal integrity issues or functional disturbance was found by upper nasal endoscopy, nasal related TEAEs, and University of Pennsylvania Smell Identification Test (UPSIT) scores. Most common TEAEs were nasal congestion (15.0%), nausea (6.8%), nasal discomfort and unpleasant taste (5.1% each) with all other TEAEs being report by < 3%. There were no treatment related Serious AEs, no cardiac TEAEs and no deaths. A total of 4,515 migraines were treated with INP104 during the 24- week treatment period (FSS). 33.1% and 49.1% of patients reported pain- and most bothersome symptom-freedom at 2 hours post-INP104 nasal delivery (Weeks 21-24, PSS) compared to 26.2% and 43.9% on best usual care at baseline, respectively. Sustained pain freedom through 24 hours was also reported in the majority of patients, as 98.4% of patients were relapse-free of their migraine after using INP104 (Weeks 21-24) compared to 93.2% using best usual care at baseline (PSS).The PAQ demonstrated that the majority of patients agreed or strongly agreed that they found INP104 easy to use (~84%) and preferred it over their current therapy (FSS).

Conclusions:

INP104 has the potential to deliver well tolerated, rapid and effective symptom relief, predictably and consistently, without injection. No new safety signals were observed following delivery to the upper nasal space. These data, along with reported patient acceptability questionnaire results, suggest INP104 may be a promising acute treatment for patients suffering from migraine.

Citation:

Shrewsbury SB, Hoekman J, Jeleva M, Hocevar-Trnka J, Hoekman J, Shrewsbury SB,
A long term, open label study of Safety and Tolerability Of Precision olfactory delivery of DHE in acute migraine (STOP 301): Clinical Results, PainWEEK Live Virtual Conference Sept 11-13, 2020