Vice President, Medical Affairs – Migraine, Impel Neuropharma

Sheena K. Aurora, MD

“Of course, DHE is not for everyone—we have contraindications in patients with cardiovascular disease and cerebrovascular disease, and those patients were excluded from STOP 301—but we also have a cardiovascular evaluation that we presented at AHS. The good news is that there are no new findings. Obviously, this has to be viewed [in the instances] where clinicians would use DHE.”

2021 Virtual American Headache Society (AHS) 63rd Scientific Annual Meeting

, June 3-6, a number of presentations were given centering around an investigational nasal formulation of a long-time migraine treatment, dihydroergotamine (DHE). This agent, developed by Impel Neuropharma, is referred to as INP104. The agent is delivered via a drug-device in a dose of 1.45 mg administered to the upper nasal space using the company’s Precision Olfactory Delivery (POD) technology.

Some of these data included the findings of the recent STOP 301 trial (NCT03557333) of INP104, which assessed the agent over a long-term period in patients with migraine. The data showed an acceptable safety profile, though safety should be monitored with intermittent use of the medication.

In an analysis of the full safety set, investigators of the study found that over 52 weeks and 6332 doses of INP104, 30 patients reported 39 nausea treatment-emergent adverse events (TEAEs; 0.6% of doses). While mild nasal congestion was not uncommon (n = 59; 16.7%), no concerning nasal or cardiovascular TEAEs were reported.

 The investigators also looked at exploratory efficacy and found that the mean number of migraine attacks (MAs) self-reported as pain- and most bothersome symptom (MBS)-free 2-hours post-INP104 ranged from 35.1% to 38.7% and 49.2% to 57.9% compared to 30.6% and 47.9% at baseline, respectively. In terms of consistency, over 24 weeks, 25%, 57%, and 59.9% of patients were 100%, 75% or greater, and 67% or greater responders, respectively.

To find out more about what the clinical community should take away from these data, 

 spoke with Sheena Aurora, MD, Vice President, Medical Affairs – Migraine, Impel Neuropharma, who presented some information about the role of DHE in treating migraine on a broad-receptor basis. She shared her insight into the data and offered her perspective on what the clinician community should note from these datsets.

REFERENCES
1. Randle L, Aurora SK, Hocevar-Trnka J, Shrewsbury SB. Reduced nausea when dihydroergotamine mesylate is delivered by INP104. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P166.
2. Craig K, Jeleva M, Hocevar-Trnka J, Aurora SK, Shrewsbury SB. Cardiovascular safety results of INP104 (POD-DHE) from the STOP 301 phase 3 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P181.
3. Davis G, Fatakia A, Pransky S, et al. Nasal safety of chronic intermittent use of INP104: Results from the phase 3 open-label STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P182.
4. Smith TR, Aurora S, Hocevar-Trnka J, Shrewsberry S. Acute treatment of migraine with INP104: exploratory efficacy from the phase 3 STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P180
5. Lipton RB, Nye BL, Hirman J, Shrewsbury SB, Aurora SK. Treatment consistency across multiple migraine attacks: results from the phase 3 open-label STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract ­P183
6. Tepper SJ, Ailani J, Shrewsbury SB, Aurora SK. Recurrence rates for INP104 for the acute treatment of migraine: results from the phase 33 STOP 301 study. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract 179.

Videos

The vice president of Medical Affairs in Migraine at Impel discussed the clinical takeaways from the STOP 301 trial of intranasal DHE and the advantages that the novel formulation might offer patients with migraine.

Clinical Takeaways From INP104 Data in Migraine: Sheena K. Aurora, MD

“Patients underwent endoscopy, so looking at it anatomically with an upper nasal endoscopy, and we did not find any issues that were related to INP104… What is good for clinicians and patients is that adverse event reporting was just as sensitive as the findings. We didn’t find any permanent changes. The most common adverse event was nasal congestion.”

In the recent STOP 301 trial (NCT03557333) of INP104, an intranasal formulation of dihydroergotamine (DHE), data suggested over the long term that it has an acceptable safety profile, though safety should be monitored with intermittent use of the medication.

Nausea is often reported with high peak plasma DHE concentration by IV administration, so the investigators sought to determine the incidence of delivery with INP104’s nasal delivery system. They analyzed data from the full safety set of 354 patients from the STOP study. Of these patients, 36.7% (n = 130) reported at least 1 treatment-related, treatment-emergent adverse event (TEAE) during the 24-week treatment period.

Sheena Aurora, MD, Vice President, Medical Affairs – Migraine, Impel Neuropharma, gave presented these findings at the 

, Aurora shared more information about Impel’s novel approach to the molecule, delivered via a drug device in a dose of 1.45 mg administered to the upper nasal space using Precision Olfactory Delivery (POD) technology. She spoke to the safety profile and the clinical relevance of the safety findings.

REFERENCE
Auruora SK. DHE Pharmacology Revisited: Does a Broad Receptor Profile Molecule Treat the Whole Migraine? Presented at AHS 2021 Scientific Annual Meeting; June 3-6.

The vice president of Medical Affairs in Migraine at Impel discussed the STOP 301 trial of intranasal DHE and how the safety profile offers a positive for patients who would use the agent on-demand.

Advantages and Safety Profile of INP104: Sheena K. Aurora, MD

“There still remains a high unmet need where DHE fits in with the patient armamentarium, particularly where there is a lot of recurrence, for patients who wake up in the morning with migraine, and patients who have menstrually associated migraine…this leads us to believe that DHE is in a unique position, and perhaps it’s the pharmacology that targets these multiple receptors that may lead to a unique position where the treatment armamentarium is concerned.”

Sheena Aurora, MD, Vice President, Medical Affairs – Migraine, Impel Neuropharma, gave a presentation at the 

, June 3-6, on the potential for novel approaches of the age-old migraine therapy dihydroergotamine (DHE) to address some of the longstanding unmet needs in the condition. Particularly, she touched on its broad receptor profile that offers an ability to potentially treat, as her presentation put it, “the whole migraine.”

, Aurora explained further how her experience as a clinician in migraine provides her a wide perspective on the use of DHE and its potential through reformulations. Specifically, she pointed to Impel’s novel approach to the molecule, INP104, which is a drug-device combination of DHE delivered in a dose of 1.45 mg administered to the upper nasal space using Precision Olfactory Delivery (POD) technology.

As well, she spoke to the on-demand nature of this type of reformulation to help patients in the in-between medication moments for migraine attacks, as well as to address the differing migraine attacks that patients may experience and in the instances that they are unable to tolerate other medications. Aurora also detailed some of the findings of the STOP 301 study of INP104.

REFERENCE
Aurora SK. DHE Pharmacology Revisited: Does a Broad Receptor Profile Molecule Treat the Whole Migraine? Presented at AHS 2021 Scientific Annual Meeting; June 3-6.

The vice president of Medical Affairs in Migraine at Impel discussed the gaps in care that novel dihydroergotamine formulations, such as INP104, might be able to fill for patients with migraine.

Sheena K. Aurora, MD

Articles

Clinical Takeaways From INP104 Data in Migraine: Sheena K. Aurora, MD

Advantages and Safety Profile of INP104: Sheena K. Aurora, MD

The Broad Receptor Profile of DHE: Sheena K. Aurora, MD